scholarly journals Evaluation of Expression Level of Apolipoprotein M as a Diagnostic Marker for Primary Venous Thromboembolism

2017 ◽  
Vol 24 (3) ◽  
pp. 416-422
Author(s):  
Abrar Ahmad ◽  
Kristina Sundquist ◽  
Bengt Zöller ◽  
Björn Dahlbäck ◽  
Johan Elf ◽  
...  

Recently, decreased levels of apolipoprotein M (ApoM) were shown to be associated with higher risk of recurrent venous thromboembolism (VTE) in male patients. However, the role of ApoM in primary VTE is unknown. We aimed in our study to analyze the plasma levels of ApoM in patients with VTE in order to evaluate the diagnostic importance of ApoM in primary VTE. A total of 357 patients with suspected first episode of VTE were recruited prospectively in the SCORE study. Plasma samples from 307 patients were available for quantifying the plasma levels of ApoM in patients with VTE using sandwich enzyme-linked immunosorbent assay method. Among the whole population, plasma levels (mean [standard deviation]) of ApoM were not significantly different between patients with VTE (0.72 [0.20]) and non-VTE patients (0.72 [0.16]), P = .99. Similarly, in regression analyses, no significant association of ApoM plasma levels with the risk of VTE was found on univariate (odds ratio [OR] =1.0, 95% confidence interval [CI] 0.21-4.84, P = .99) and multivariate analysis (OR = 1.25, 95% CI = 0.19-8.34, P = .819) after adjusting for age, body mass index, and smoking. Moreover, results did not differ significantly after stratification of data according to sex ( P > .05). In this study, our results do not suggest a diagnostic role for ApoM plasma levels in patients with primary VTE. Moreover, the current study suggests that role of ApoM as a risk factor may differ for primary VTE and recurrent VTE in male patients.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hongseok Yoo ◽  
Yunjoo Im ◽  
Ryoung-Eun Ko ◽  
Jin Young Lee ◽  
Junseon Park ◽  
...  

AbstractThe role of high-mobility group box-1 (HMGB1) in outcome prediction in sepsis is controversial. Furthermore, its association with necroptosis, a programmed cell necrosis mechanism, is still unclear. The purpose of this study is to identify the association between the plasma levels of HMGB1 and the severity and clinical outcomes of sepsis, and to examine the correlation between HMGB1 and key executors of necroptosis including receptor-interacting kinase 3 (RIPK3) and mixed lineage kinase domain-like- (MLKL) proteins. Plasma HMGB1, RIPK3, and MLKL levels were measured with the enzyme-linked immunosorbent assay from the derivation cohort of 188 prospectively enrolled, critically-ill patients between April 2014 and December 2016, and from the validation cohort of 77 patients with sepsis between January 2017 and January 2019. In the derivation cohort, the plasma HMGB1 levels of the control (n = 46, 24.5%), sepsis (n = 58, 30.9%), and septic shock (n = 84, 44.7%) groups were significantly increased (P < 0.001). A difference in mortality between high (≥ 5.9 ng/mL) and low (< 5.9 ng/mL) HMGB1 levels was observed up to 90 days (Log-rank test, P = 0.009). There were positive linear correlations of plasma HMGB1 with RIPK3 (R2 = 0.61, P < 0.001) and MLKL (R2 = 0.7890, P < 0.001). The difference in mortality and correlation of HMGB1 levels with RIPK3 and MLKL were confirmed in the validation cohort. Plasma levels of HMGB1 were associated with the severity and mortality attributed to sepsis. They were correlated with RIPK3 and MLKL, thus suggesting an association of HMGB1 with necroptosis.


2011 ◽  
Vol 3 ◽  
pp. BIC.S7154 ◽  
Author(s):  
Veyis Itik ◽  
Ozgur Kemik ◽  
Ahu Kemik ◽  
A. Cumhur Dulger ◽  
Aziz Sümer ◽  
...  

Aims and background YKL-40 is secreted by several types of tumors. Increased serum YKL-40 levels have been reported in prostate, glioblastoma, breast and colorectal cancers. Determination of YKL-40 levels may serve as a valuable biomarker for the diagnosis and treatment of gastric cancer. The purpose of this study was to determine the serum YKL-40 levels expressed in gastric carcinomas. Methods Between 2009 and 2011, we retrospectively reviewed 100 patients with gastric cancer and compared their serum samples to 75 healthy volunteers. YKL-40 levels were determined by an enzyme-linked immunosorbent assay (ELISA). Results We found significantly higher serum levels of YKL-40 in patients with gastric cancer compared to the healthy population ( P < 0.0001). We also found significant differences in serum YKL-40 levels between female and male patients with gastric cancer ( P < 0.01). Conclusions YKL-40 is over-expressed in gastric cancer, suggesting a more aggressive phenotype. YKL-40 may be a useful serum biomarker for gastric cancer identification, and future studies should focus on the role of YKL-40 in the tumorigenesis of gastric cancer and responsiveness toward treatment.


2018 ◽  
Vol 24 (8) ◽  
pp. 1223-1233 ◽  
Author(s):  
Stephen Statz ◽  
Giselle Sabal ◽  
Amanda Walborn ◽  
Mark Williams ◽  
Debra Hoppensteadt ◽  
...  

It has been well established that angiopoietin 2 (Ang-2), a glycoprotein involved in activation of the endothelium, plays an integral role in the pathophysiology of sepsis and many other inflammatory conditions. However, the role of Ang-2 in sepsis-associated coagulopathy (SAC) specifically has not been defined. The aim of this study was to measure Ang-2 plasma levels in patients with sepsis and suspected disseminated intravascular coagulation (DIC) in order to demonstrate its predictive value in SAC severity determination and 28-day mortality outcome. Plasma samples were collected from 102 patients with sepsis and suspected DIC at intensive care unit (ICU) admission. The Ang-2 plasma levels were quantified using a sandwich enzyme-linked immunosorbent assay method. The International Society on Thrombosis and Haemostasis DIC scoring system was used to compare the accuracy of Ang-2 levels versus clinical illness severity scores in predicting SAC severity. Mean Ang-2 levels in patients with sepsis and DIC were significantly higher in comparison to healthy controls ( P < 0.0001), and median Ang-2 levels showed a downward trend over time ( P = 0.0008). Baseline Ang-2 levels and clinical illness severity scores were higher with increasing severity of disease, and Ang-2 was a better predictor of DIC severity than clinical illness scores. This study demonstrates that Ang-2 levels are significantly upregulated in SAC, and this biomarker can be used to risk stratify patients with sepsis into non-overt DIC and overt DIC. Furthermore, the Ang-2 level at ICU admission in a patient with sepsis and suspected DIC may provide a predictive biomarker for mortality outcome.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1041-1041
Author(s):  
Kazuo Kawasugi ◽  
Maho Noguchi ◽  
Haruko Tashiro ◽  
Moritaka Gotoh ◽  
Naoki Shirafuji ◽  
...  

Abstract Injury of endothelial cells has been postulated as an initial trigger of the progression of DIC. Although hepatocyte growth factor (HGF) is a member of endothelium-specific growth factor, the relationship between HGF and DIC has not been described. To investigate the role of HGF, we measured plasma levels of HGF in patients with sepsis-associated (n=20) and acute promyelocytic leukemia (APL)-induced DIC (n=6). Plasma samples from those patients groups were assayed for HGF levels by enzyme-linked immunosorbent assay (ELIZA, TECHNE Corporation, USA). The VEGF levels were determined by one-step sandwich enzyme immunoassay (EIA, Chemicon International, USA). The thrombin antithrombin complexes (TAT) levels were higher in both DIC patients as reported by others. In the septic patients with DIC, we found significant elevations in HGF levels compared to normal controls. Also, the HGF levels were elevated in the APL patients with DIC. However, we did not find any difference in plasma levels of VEGF in the APL and septic patients with DIC. There was a slight correlation between the TAT and HGF levels in both (septic and APL) patients groups with DIC. These results suggest that plasma levels of HGF may be candidates for a marker of DIC. It appears that HGF may contribute to the severity of DIC. Sepsis associated DIC APL with DIC Controls (n=10) *(P<0.005) significantly different controls HGF 7949±71230* 11902±10726 846±216pg/ml VEGF 172±7.0 209±35 188±8pg/ml TAT 28.4±17.5* 22.5±15.3* <3 μg/ml


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3348-3348
Author(s):  
Luis Fernando Bittar ◽  
Bruna Mazetto Fonseca ◽  
Silmara Lima Montalvão ◽  
Fernanda Loureiro de Andrade Orsi ◽  
Erich V de Paula ◽  
...  

Abstract Abstract 3348 Introduction: Venous thromboembolism (VTE) is a multifactorial disease, and increased levels of coagulation factor VIII (FVIII) has been demonstrated as risk factor for first and recurrent episodes of VTE. Some authors reported that these high levels of FVIII were still persistent after 4 years of the episode, but median follow-up in these studies are relatively short. The aim of the study was investigate if after a long-term follow-up of 4–15 years (median of 10 years), patients with high levels of FVIII after anticoagulant treatment still showed this alteration. Design and Methods: Previously, we selected 174 adult patients with a first episode of acute VTE between January 1990 and September 2004. One hundred seventy four healthy adult individuals selected from blood donors were chosen as controls, from the same geographic area of origin. Of this group of VTE patients, 68 patients with plasma FVIII: C levels above the 90th percentile were selected. FVIII levels (FVIII:C) were measured by a one-stage clotting assay with FVIII-deficient plasma in duplicate in an automated coagulometer. Levels were measured twice, in 2004 and then in 2011. C-reactive protein (CRP) levels were determined in the same samples by a nephelometric method to evaluate the influence of inflammation on FVIII levels. For individuals with CRP values higher than 1mg/dL, an additional blood sample was analyzed. High FVIII levels were only considered for further analysis when in the presence of normal CRP levels. The presence of post-thrombotic syndrome (PTS) was evaluated and classified clinically by the Clinical-Etiologic-Anatomic-Pathophysiologic (CEAP) classification System. Results: 68 patients with VTE and high levels of FVIII (19M:49F) with a median age of 47 years (range 20–70) were included in the study. The control group consisted of 59 subjects (42M:17F) with a median age of 35 years (range 21–56 years). VTE was spontaneous in 26 (38.2%) patients and secondary to an acquired risk factor in 61.8%. In the 1st evaluation, in 2004, patients with VTE had higher plasma levels of FVIII:C (median 235.8 IU/dL vs. 127.0 IU/dL; p<0.001) compared to controls. In 2011, seven years after the first evaluation and after a median follow-up of 10 years after the first VTE episode, this difference was still present (median 144.6 IU/dL vs. 96.4 IU/dL; p<0.001). Patients with severe PTS (167 IU/dL) showed higher plasma levels of FVIII when compared with patients without PTS (median 141.4 IU/dL), mild PTS patients (median 142.8 IU/dL), and moderate PTS patients (median 143.2); p=0.04. Conclusions: Our results show that even after a median of 10 years of VTE, patients still have increased levels of FVIII. Moreover, there seems to be a relationship between severe post-thrombotic syndrome and increased plasma levels of FVIII. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Raif ALAN ◽  
◽  
Onur GEZGİN ◽  
Emre KORKUT ◽  
Şükriye TÜRKOĞLU ◽  
...  

Objective: This study aimed to assess the effect of passive tobacco smoking (PTS) through the comparison of the periodontal status and the C-reactive protein (CRP) and cotinine levels in the biologic fluids in children who are exposed and unexposed to PTS. Methods: A total of 148 participants, whom had smokers (PTS-exposed, n=82) and non-smokers (PTS-unexposed, n=66) in their families, respectively, were included in the study. Gingival index, plaque index, probing depth, and bleeding on probing were recorded. Moreover, saliva, urine, and gingival crevicular fluid samples were collected. CRP and cotinine levels in the biological fluids were determined by the enzyme-linked immunosorbent assay method. Results: Both groups exhibited similar values for periodontal parameters and salivary CRP levels were higher in PTS-exposed group but not significant. The mean urinary cotinine level was significantly higher in children exposed to PTS than in unexposed children. Conclusions: There was no evidence for causative role of PTS in periodontal disease in this study. Longitudinal studies including large populations should be conducted to provide stronger evidence for the causative role of PTS in periodontal disease. Also, further epidemiological studies on the social context of smoking should be performed to improve the quality of life and lifespan of the society


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Lita A Freeman ◽  
Robert Shamburek ◽  
Angel Aponte ◽  
Gregory J Kato ◽  
Alan T Remaley

BACKGROUND: Apolipoprotein M (apoM) is a 25 kD plasma protein present mainly in HDL. It has a hydrophobic pocket for carrying ligands variously reported as retinol, all- trans -retinoic acid, 9- cis -retinoic acid, sphingosine-1-phosphate (S1P) and oxidized phospholipids. In addition to mediating the effects of S1P and modulating oxidative stress, apoM has been reported to enhance cholesterol efflux and to increase plasma levels of small, preβ1 HDL, a particle that efficiently accepts cholesterol effluxed from cholesterol-loaded cells and plays a key role in reverse cholesterol transport. ApoM is present in α-migrating HDL particles but whether it is also present in small preβ1 HDL particles is disputed. Establishing the absence or presence of apoM in preβ1 HDL particles is essential for understanding its role in reverse cholesterol transport. METHODS: We performed native-native 2D gel electrophoresis on healthy volunteer plasma to separate native HDL particles by size and charge. Particles were blotted onto a membrane and probed with antibodies to apoM or apoA-I to identify specific HDL particles associated with apoM. Similar experiments were performed with plasma from patients with apoE-deficiency or from patients with low plasma levels of apoA-I and HDL. We also performed native 1D electrophoresis to visualize lipoprotein particles containing apoM. Finally, native-native 2D gels of purified HDL were used for proteomics of preβ1 particles. RESULTS: apoM was present in two large α-migrating HDL particles and in LDL-sized particles, as well as in one small particle that did not contain apoA-I. apoA-I but not apoE was required for formation of the large apoM-containing HDL particles. The small apoM particle was unaffected in apoA-I- and apoE-deficient patients. apoM was not present in preβ1 particles. CONCLUSION: apoM is not a stable component of small preβ1 apoA-I-containing HDL particles but instead resides mainly in two large HDL molecules and in LDL-sized particles, as well as a small particle that does not contain apoA-I. The role of apoM in cholesterol efflux requires further evaluation.


2007 ◽  
Vol 18 (4) ◽  
pp. 207-215 ◽  
Author(s):  
Candan Öztürk ◽  
Aynur Özge ◽  
Osman Özgür Yalın ◽  
&Idot;. Arda Yılmaz ◽  
Nuran Delialioglu ◽  
...  

In the past years, the possible involvement of inflammation in the pathogenesis of dementia has been the subject of several investigations. However there are restricted data about the profile of the inflammatory and soluble proteins in well evaluated Alzheimer’s disease (AD), vascular dementia (VD), mild cognitive impairment (MCI) and healthy controls. There are also no reliable data regarding the relationship between the overlapping protein levels and cognitive or functional decline. We measured levels of IL-1β, IL-2, IL-6, IL-18, TNF-α,β-Amlyloid 1–40 andα1-antichymotrypsin levels in plasma in groups of total 82 subjects with AD, MCI, VD and controls using enzyme-linked immunosorbent assay (ELISA) method. Our study samples showed high levels of proinflammatory cytokine levels (especially IL-18) in all patient groups but only high levels ofα1-antichymotrypsine in VD patients compared to controls. There is no significant correlation between the laboratory and clinical variables except for a link between IL-1βand NPI scores of AD. In conclusion, this study yielded evidence of some shared mechanisms underlying AD and VD and thus motivates further studies of inflammatory markers in various types of dementia and MCI.


2019 ◽  
Vol 119 (05) ◽  
pp. 834-843 ◽  
Author(s):  
Aaron Folsom ◽  
Weihong Tang ◽  
Saonli Basu ◽  
Jeffrey Misialek ◽  
David Couper ◽  
...  

AbstractThe kallikrein/kinin system, an intravascular biochemical pathway that includes several proteins involved in the contact activation system of coagulation, renin–angiotensin activation and inflammation, may or may not play a role in venous thromboembolism (VTE) occurrence. Within a large prospective population-based study in the United States, we conducted a nested case–cohort study to test the hypothesis that higher plasma levels of high molecular weight kininogen (HK) or prekallikrein are associated with greater VTE incidence. We related baseline enzyme-linked immunosorbent assay measures of HK and prekallikrein in 1993 to 1995 to incidence VTE of the lower extremity (n = 612) through 2015 (mean follow-up = 18 years). We found no evidence that plasma HK or prekallikrein was associated positively with incident VTE. HK, in fact, was associated inversely and significantly with VTE in most proportional hazards regression models. For example, the hazard ratio of VTE per standard deviation higher HK concentration was 0.88 (95% confidence interval = 0.81, 0.97), after adjustment for several VTE risk factors. Our findings suggest that plasma levels of these factors do not determine the risk of VTE in the general population.


Blood ◽  
1993 ◽  
Vol 82 (10) ◽  
pp. 3177-3182 ◽  
Author(s):  
P Gessler ◽  
N Kirchmann ◽  
R Kientsch-Engel ◽  
N Haas ◽  
P Lasch ◽  
...  

Abstract The neonate is uniquely susceptible to severe and overwhelming bacterial infections. One of the most important deficits in the neonatal host defense system seems to be a quantitative and qualitative deficiency of the myeloid and the phagocytic system. Future optimal therapy of neonatal sepsis may include the use of adjuvant immunologic therapy. Granulocyte colony-stimulating factor (G-CSF) has been shown to induce neutrophilia and to enhance mature effector neutrophil function. To evaluate the role of G-CSF with respect to infection, we examined serum levels of G-CSF in term and preterm neonates, using an enzyme-linked immunosorbent assay method. G-CSF levels in healthy neonates showed peak levels up to 7 hours after birth, followed by an increase in total neutrophil cell (TNC) counts. Both G-CSF levels determined between 4 and 7 hours after birth and peak TNC counts correlated with the gestational age of the neonates. The state of nutrition, maternal treatment with glucocorticoids, maternal infection and hypertension, and the mode of delivery influenced peak G-CSF levels. Neonates with signs of infection between 4 and 7 hours after birth had higher levels of G-CSF than did healthy neonates (1,312 +/- 396 pg/mL v 176 +/- 19 pg/mL). In conclusion, the presented results of serum concentrations of G-CSF in relation to TNC counts and various diseases suggests an important role of G-CSF in the regulation of granulopoiesis during the neonatal period.


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