Oxidative modification of patient's plasma proteins and its role in pathogenesis of multiple sclerosis

BackgroundOxidative stress plays an important role in multiple sclerosis (MS).Objective and methodsThe present study was designed to evaluate the modifications of plasma proteins by estimation markers of oxidative/nitrosative stress: carbonyl groups and 3-nitrotyrosines (3-NT) levels in relapsing-remitting (RR) (n = 10) and secondary progressive (SP) (n = 10) clinical course of multiple sclerosis. Moreover, we estimated the level of uric acid (UA) in plasma of MS patients.ResultsCompared to controls (n = 10), the levels of carbonyl groups in plasma proteins were elevated (P < 0.0001) as well in RRMS as in SPMS. The highest concentration of 3-NT was observed in plasma proteins obtained from SPMS patients (P < 0.0005). The level of uric acid in plasma was significantly lower in RRMS (P < 0.0001) than SPMS.ConclusionThis is the first report which presented differences between SPMS and RRMS patients in 3-NT and protein carbonyl groups in plasma proteins.     

Specific increase in serum autotaxin activity in patients with pancreatic cancer

ObjectivesTo evaluate the potential clinical significance of serum autotaxin (ATX) level in patients with cancers of the digestive system.Design and methodsSerum ATX activity was measured as the lysophospholipase D activity in patients with cancer of the esophagus (n = 8), stomach (n = 18), colorectum (n = 21), biliary tract (n = 19), or pancreas (n = 103) and in patients with benign pancreatic diseases (n = 73).ResultsAmong patients with various cancers of digestive system, increased serum ATX activity was predominantly observed among pancreatic cancer patients. Serum ATX activity was not increased in patients with chronic pancreatitis or pancreatic cysts. In the diagnosis of pancreatic cancer, the area under the receiver operating curve for serum ATX activity was 0.541 (95% CI, 0.435–0.648) for men and 0.772 (95% CI, 0.659–0.885) for women. No significant correlation was observed between serum ATX activity and CEA, CA19-9 or Dupan2 levels.ConclusionSerum ATX activity may be useful for identifying pancreatic cancer when used together with other serum markers of pancreatic cancer.     

Cytokine elevations in acute coronary syndrome and ovarian cancer: a mechanism for the up-regulation of the acute phase proteins in these different disease etiologies

Objectives:To identify if a common set of cytokines is elevated in both ovarian cancer and acute coronary syndrome (ACS).Design and methods:A cytokine array (Randox Ltd) was measured in healthy women (n = 33), women with ACS (n = 21) and ovarian cancer (n = 45).Results:Women with ACS or ovarian cancer had higher concentrations of IL-6, IL-8, VEGF, MCP-1, and EGF as compared to healthy volunteers.Discussion:Common cytokine elevations are present in both ACS and ovarian cancer.     

Serum soluble Fas levels in patients with autoimmune rheumatic diseases

Objective:The role of the serum soluble Fas (sFAS) system is unclear in diagnosis of several autoimmune rheumatic diseases although there are present contradictory reports on the levels of serum sFas. We therefore assessed levels of sFAS in serum of patients with autoimmune rheumatic diseases.Patients and methods:We analyzed sFas levels and their relationship to clinical and laboratory data in patients with systemic lupus erythematosus (SLE, n = 32), rheumatoid arthritis (RA, n = 28), Sjögren's syndrome (SS, n = 20) systemic sclerosis (SSc, n = 21), polymyositis/dermatomyositis (PM/DM, n = 15). Patients with osteoarthritis (OA, n = 20) and healthy volunteers (n = 20) were used as controls. Serum levels of sFAS were determined by ELISA. sFas levels greater than mean (normals) + 2 SD were considered as elevated.Results:The mean sFas values were found higher in RA, PM/DM and OA than in control although no differences were found in SSc and SS patients. The mean sFas levels in SLE patients were lower than healthy controls. Elevated sFas rates in RA, PM/DM and SS were found to be 21.4%, 60%, 10% higher than in healthy controls, respectively. sFas levels in SLE and SSc did not differ from control values. Mean sFas levels did not show significant difference between active and inactive patients in all disease groups except PM/DM, RA and OA. No correlations of sFas with relevant disease subsets, laboratory findings and treatment modalities were found.Conclusions:The findings indicate that the serum sFas molecule may provide a useful additional marker for presence and assessment of disease in patients with RA and PM/DM.     

Measurement of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 after delayed separation of whole blood samples

Objectives:Epidemiological studies benefit from unbiased blood specimens collected with minimal cost and effort of blood collection and storage. We evaluated the stability of IGF-1 and IGFBP-3 in whole blood samples stored at room temperature to justify delays in blood processing.Design and methods:Total IGF-1 and IGFBP-3 levels were measured in EDTA plasma (n = 12), heparin plasma (n = 12) and serum (n = 10) samples of healthy volunteers after blood processing delays up till 14 days. Stability of measured IGF-1 and IGFBP-3 levels was tested by paired t-test and a linear mixed effect model.Results:Longitudinal analysis showed that IGF-1 levels were not significantly affected by blood processing delays in EDTA tubes (p = 0.18) and IGFBP-3 levels were marginally stable (p = 0.06). In heparin plasma and serum, however, IGF-1 increased over time of delayed processing and IGFBP-3 levels tended to decrease (p < 0.01).Conclusion:Total IGF-1 and IGFBP-3 levels are stable in whole blood collected in EDTA tubes at room temperature up till 7 days, allowing a delay in blood processing to reduce costs in large multi-center studies.     

Xanthine oxidase activity in patients with sepsis

ObjectiveDetermine the relation of xanthine oxidase (XO) activity and the outcome of septic patients and its relation to oxidative damage and clinical parameters of sepsis severity.Design and methodsPatients admitted over a 6-month period were enrolled. Patients were assigned to groups according to the diagnosis of sepsis (n = 8), severe sepsis (n = 28) or septic shock (n = 36). Blood samples were collected to the determination of thiobarbituric acid reactive species (TBARS), protein carbonyls and XO activity.ResultsNone of the studied oxidative parameters determined at the time of diagnosis were related to sepsis severity. XO activity, but not oxidative damage parameters, at the time of sepsis diagnosis was significantly higher in non-survival septic patients. In contrast, 24 h after sepsis diagnosis, XO activity was lower in non-survivors septic patients.ConclusionsXO activity was increased in non-survivors patients and the variations in XO activity could be used for outcome prediction.     

Tools for measuring the impact of informal caregiving of the elderly: a literature review

Objectives(1) Describe available tools to assess the impact of informal caregiving of home-dwelling elderly, (2) identify an acceptable and appropriate tool for a study aiming at the evaluation of the impact of innovative projects for care and support of care for elderly at home, on their main informal caregiver and (3) find a definition of ‘main informal caregiver’.Study designLiterature review by searches of the following electronic databases: MEDLINE, CINAHL, EMBASE, using firstly keywords and exclusion criteria, then citations and reference search.ResultsThis review has identified 105 scales assessing the impact of informal caregiving of the elderly. Those scales were described in terms of characteristics of the care receiver population, content and psychometric properties. Most retrieved scales are intended to measure the impact of caregiving on caregivers’ health of elderly with dementia (n = 49), overall elderly (n = 21), cancer patients (n = 7), chronically ill patients (n = 7), psychiatric patients (n = 7) and stroke patients (n = 3).Dimensions of the impact of caregiving were classified into its positive (n = 34), negative (n = 55) or neither positive nor negative (n = 16) consequences on the informal caregiver's health. Internal consistency varied from 0.48 to 0.99 and in half of the cases (n = 52), construct validity was reported. Scales comprised 1–200 questions. The Zarit Burden Interview (ZBI-12) was selected for the study and an operational definition of the concept of “main informal caregiver” was constructed.ConclusionThis review identified a large number of scales that can be used to assess the impact of caregiving, viewed through different dimensions. The Zarit Burden Interview can be a useful tool for researchers and clinicians due to its user-friendliness, extensively validation and international use, making comparisons between groups possible. Despite the fact that only the original version of each scale was selected, this inventory should be a useful tool for intervention studies and even clinicians work.     

Natriuretic peptide precursor B gene (TTTC)(n) microsatellite polymorphism in pre-eclampsia

BackgroundThere is a variable tandem repeat polymorphism in the 5′-flanking region of the natriuretic peptide precursor B gene (NPPB). A previous study showed association of the (TTTC) small tandem repeat (STR) variants of this gene and essential hypertension. Our aim was to identify this polymorphism in samples of pre-eclamptic patients and healthy controls. We also compared the natriuretic peptide B (BNP) concentrations.MethodsBlood samples were collected from healthy pregnant normotensive women (n = 235) and women with pre-eclampsia (n = 220). DNA was isolated and fluorescent PCR and DNA fragment analysis was performed for the detection of (TTTC) repeats. The plasma BNP concentration was measured by fluorescence immunoassay method.ResultsWe detected 12 different (TTTC) repeats on the NPPB gene in the studied population. The overall distribution of alleles and genotypes was significantly different between the control and pre-eclamptic groups. The number of 10-repeat genotype carriers showed significantly lower frequency in pre-eclamptics than in the healthy pregnant controls (p = 0.032). After adjustment for confounding factors pre-pregnancy BMI, maternal age, primiparity and smoking, the calculated odds ratio (OR) was 0.19 (95% CI: 0.04–0.87). Similarly, the 12-repeat genotype carriers showed significantly lower frequency in pre-eclamptics than in the healthy pregnants (p = 0.037; adjusted OR: 0.53 (95% CI: 0.29–0.96)). In contrast the 11-repeat genotype carrier frequency was significantly higher in the pre-eclamptic than in the healthy pregnant group (p < 0.001; adjusted OR 2.91 (95% CI: 1.75–4.84)).The concentration of the BNP was 9.75 pg/ml in the healthy controls and 32.40 pg/ml in the pre-eclamptic group (p < 0.0001). The 11/11 genotype carriers had significantly higher BNP levels in both groups.ConclusionsThe NPPB gene (TTTC) microsatellite polymorphism in the 5′-flanking region showed significant difference in the distribution of alleles and genotypes between healthy pregnant controls and pre-eclamptic patients in an ethnically homogeneous population. The concentration of the BNP was higher in pre-eclamptic women, and it showed association with the (TTTC) genotypes. We introduced an F-PCR and DNA fragment analysis method for the fast and reliable detection of this STR.     

Plasma adiponectin as an independent predictor of early death after acute intracerebral hemorrhage

BackgroundHyperadiponectinemia or hypoadiponectinemia is associated with different diseases. There is a paucity of data on circulating plasma adiponectin concentrations in human intracerebral hemorrhage (ICH). We investigated the plasma adiponectin concentrations in patients with intracerebral hemorrhage, and analyzed the correlation of adiponectin with the severity of brain injury and early mortality after ICH.MethodsThirty controls and 86 patients with acute ICH were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7 after ICH. Their concentrations were measured by enzyme-linked immunosorbent assay.ResultsAfter ICH, plasma adiponectin level of the patients increased immediately within 6 h, peaked within 24 h, plateaued at day 2, and decreased gradually thereafter. It was substantially higher than that in the controls in a period of 7 days. A multivariate analysis showed plasma adiponectin level was an independent predictor for 1-week mortality (odds ratio, 1.199; 95% CI: 1.035–1.389; P = 0.015) and that it was associated with Glasgow coma scale (GCS) score (t = ? 3.596, P = 0.001) and plasma C-reactive protein level (t = 4.194, P < 0.001). A receiver operating characteristic curve identified that a plasma adiponectin level > 16.4 μg/ml predicted the 1-week mortality of patients with a sensitivity of 65.6% and a specificity of 90.7% (AUC, 0.789; 95% CI: 0.688–0.870). The predictive value of adiponectin concentration was significantly lower than that of GCS score (P = 0.007) and hematoma volume (P = 0.022). Adiponectin could not improve the predictive values of GCS score (P = 0.317) and hematoma volume (P = 0.226).ConclusionsAdiponectin is an independent indicator of early death and may play an anti-inflammatory role after intracerebral hemorrhage.     

It Is “Too Late” or Is It? Bereaved Family Member Perceptions of Hospice Referral When Their Family Member Was on Hospice for Seven Days or Less

ContextMany family members of patients enrolled in hospice for less than seven days state that the hospice referral was made “at the right time.”ObjectivesTo examine bereaved family members’ perceptions of the timing of hospice referral to identify aspects of the referral process that can be improved.MethodsOpen-ended interviews were conducted in seven hospice programs, interviewing bereaved family members of hospice patients who died within the first week of hospice enrollment.ResultsOf the 100 narrative interviews, 99 respondents stated that their family member was either referred “too late” (n = 41) or “at the right time” (n = 58) to hospice services. When families stated that referral was “at the right time,” their perceptions were based on the patient having refused earlier referral (n = 8), a rapid decline in the patient’s condition resulting in the late referral (n = 20), or a belief in all things coming together as they were meant to (n = 11). In contrast, when families stated that referral was “too late,” their reasons were centered on concerns with the health care providers’ role in decision making (n = 24), with the leading concerns being inadequate physician communication (n = 7), not recognizing the patient as dying (n = 11), or problematic hospice delays in referral from the nursing home or home health agency (n = 4). Despite the patient refusing an earlier hospice referral, five family members believed the referral was “too late.”ConclusionWhereas family members identified expected concerns with communication, more than one in three stated an earlier hospice referral was not possible.     

Lymphocytic enzymes and lipid peroxidation in patients with metabolic syndrome

ObjectivesMetabolic syndrome (MetS) is considered a state of chronic inflammation. This study aimed to ascertain selected parameters of purinergic and cholinergic systems related to glucose metabolism and inflammation, as well as _γ-glutamyltransferase (GGT) and N-acetyl-b-glucosaminidase (NAG) activities and lipoperoxidation in lymphocytes of patients with MetS.Design and methodsThe adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), acetylcholinesterase (AChE), GGT and NAG activities, as well as thiobarbituric acid reactive substances (TBARS) levels were investigated in lymphocytes of patients with MetS (n = 38) and healthy volunteers (n = 41). We also evaluated the insulin levels, anthropometric measurements and routine biochemical analyses.ResultsADA (p < 0.05), DPP-IV and AChE (p < 0.0001) activities were higher in patients with MetS when compared to the control group. Furthermore, we observed correlations between ADA and DPP-IV activities (p = 0.0002; r = 0.5945), TBARS levels and ADA (p = 0.0021; r = 0.5172) and DPP-IV activities (p = 0.0022; r = 0.5010).ConclusionsOur findings showed that MetS might cause tissue distress that disturbed lymphocytic ADA, DPP-IV and AChE activities in response to inflammatory stimuli. These alterations evidence clinical abnormalities, since these enzymatic systems are able to regulate several aspects of adipose tissue function and inflammatory state of MetS and could be used successfully both for preventing and for halting the progression of MetS.     

High resolution melting analysis for the detection of SLC25A13 gene mutations in Taiwan

BackgroundCitrin, encoded by SLC25A13 gene, is a mitochondrial solute transporter with a crucial role in urea, nucleotide and protein synthesis. SLC25A13 mutations cause two phenotypes, adult-onset type II citrullinemia and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). This study aimed to develop a high resolution melting (HRM) analysis for SLC25A13 mutation scanning and determine the carrier rate in Taiwan.MethodsDNAs from healthy subjects (n = 479), and patients with hepatocellular carcinoma (HCC, n = 100) and NICCD (n = 5) were scanned in exons 6, 9, 11, 16, and 17 and parts of introns of SLC25A13 using HRM analysis. All mutations detected by HRM analysis were further confirmed by TaqMan method and/or direct sequencing.ResultsIn healthy subjects, seventeen carriers with mutants c.851_854del (n = 10), c.1638_1660dup, c.615 + 5G > A (n = 4), and two novel mutants, c.475C > T and c.1658G > A, were detected. The frequency of carriers was about 1/28. In patients with HCC, there were only 2 carriers with c.851_854del mutant. Patients with NICCD (n = 5) diagnosed during 2007 and 2008, harbored compound heterozygous mutations c.851_854del/c.1177 + 1G > A, c.851_854del/c.1638_1660dup (n = 2), c.851_854del/c.615 + 5G > A, and c.1638_1660dup/c.615 + 5G > A.ConclusionsHRM analysis is a simple, rapid and robust method for detecting SLC25A13 mutations in clinical laboratories. SLC25A13 mutations may not be a major contributor to the pathogenesis of HCC in Taiwan.     

Anticoagulants affect matrix metalloproteinase 9 levels in blood samples of stroke patients and healthy controls

ObjectivesMatrix metalloproteinase-9 (MMP-9) represents a promising marker for acute stroke management. In clinical studies MMP-9 has been quantified by ELISA using differing protocols. We aimed to establish a valid protocol by evaluation of preanalytics.Design and methodsBlood from stroke patients (n = 28) and healthy controls (n = 28) was drawn into tubes containing different anticoagulants (EDTA, citrate, lithium-heparin (heparin) and heparin with proteinase inhibitors) and processed after 0, 60 and 240 min. MMP-9 plasma protein and mRNA from mononuclear leukocytes were determined.ResultsIn regard to anticoagulants used, samples showed different MMP-9 protein baseline values and kinetics. Stable MMP-9 protein concentrations were only measured from EDTA samples. Particularly in samples with proteinase inhibitors protein and mRNA concentrations increased over time. Kinetics did not differ between patients and controls.ConclusionsPreanalytics plays a key role for determination of MMP-9. EDTA seems to be a valid anticoagulant for MMP-9 protein measurement.     

Patient selection has a strong impact on cystatin C and Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rate

ObjectiveEstimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with kidney disease, and for correct dosage of drugs that are eliminated from the circulation by the kidneys. In most cases GFR is estimated based on serum creatinine and the Modification of Diet in Renal Disease (MDRD) formula. As both cystatin C and creatinine are used for the determination of GFR it is important to investigate if estimated GFR by the two methods differ in various patient groups.Design and methodsWe have compared cystatin C and MDRD estimated GFR calculated from the same request from primary care units (n = 488), a cardiology ward (n = 826), the cardiointensive care unit (n = 1026), two oncology wards (n = 919 and 1021), and the neurosurgical intensive care unit (n = 1515) in an observational cross-sectional study.ResultsWe found better agreement between the two GFR estimates in samples from primary care patients and patients in the cardiology wards, than in samples from oncology wards or the neurosurgical intensive care unit. In the latter settings there was a pronounced difference between the two GFR estimates.ConclusionThe comparisons show that differences in patient selections have a strong impact on the agreement between cystatin C and MDRD estimated glomerular filtration rate.     

Prediction of the neurological outcome with intrathecal high mobility group box 1 and S100B in cardiac arrest victims: a pilot study

ObjectivesTo investigate whether high mobility group box 1 (HMGB1) and S100B in cerebrospinal fluid (CSF) and the serum predict the neurological outcome in patients resuscitated from out-of-hospital cardiac arrest (OHCA).Materials and methodsThis study was designed as a prospective observational study. Twenty-five patients, who received standard cardiopulmonary resuscitation and post-resuscitation intensive care, were enrolled in this study. The patients were divided into two groups according to Glasgow-Pittsburgh Cerebral Performance categories (CPCs) at 6 months after return of spontaneous circulation (ROSC), Group G (n = 7, CPC 1 or 2) and Group P (n = 18, CPC ≥ 3). Their blood samples were taken at 6, 24, and 48 h after ROSC. The patients, whose CSF was sampled at 48 h, were also divided into either sub-Group G (n = 6) or sub-Group P (n = 8) at 6 months after ROSC.ResultsHMGB1 and S100B in CSF in sub-Group P were significantly higher than those in sub-Group G (HMGB1, <1.0 vs. 12.4 ng/ml, P = 0.009; S100B, 2.68 vs. 84.2 ng/ml, P = 0.007, respectively). HMGB1 in CSF was strongly correlated with S100B (σ = 0.81, P = 0.001). HMGB1 was elevated in serum at 6 h and normalized within 48 h after ROSC without any significant differences between the two groups. Serum S100B in Group P was significantly higher than that in Group G at each time point.ConclusionsThe significant elevations of HMGB1 and S100B in CSF, and S100B in serum are associated with the neurologically poor outcome in OHCA patients.     

HDL-C concentration is related to markers of absorption and of cholesterol synthesis: Study in subjects with low vs. high HDL-C

BackgroundThe antiatherogenic functions of high density lipoprotein (HDL-C) include its role in reverse cholesterol transport, but to what extent the concentration of HDL-C interferes with the whole-body cholesterol metabolism is unknown. Therefore, we measured markers of body cholesterol synthesis (desmosterol and lathosterol) and of intestinal cholesterol absorption (campesterol and β-sitosterol) in healthy subjects that differ according to their plasma HDL-C concentrations.MethodsHealthy participants presented either low HDL-C (< 40 mg/dl, n = 33, 17 male and 16 female) or high HDL-C (> 60 mg/dl, n = 33, 17 male and 16 female), BMI < 30 kg/m², were paired according to age and gender, without secondary factors that might interfere with their plasma lipid concentrations. Plasma concentrations of non-cholesterol sterols were measured by the combined GC–MS analysis.ResultsPlasma desmosterol did not differ between the two groups; however, as compared with the high HDL-C participants, the low HDL-C participants presented higher concentration of lathosterol and lower concentration of the intestinal cholesterol absorption markers campesterol and β-sitosterol.ConclusionPlasma concentrations of HDL, and not the activities of LCAT and CETP that regulate the reverse cholesterol transport system, correlate with plasma sterol markers of intestinal cholesterol absorption directly, and of cholesterol synthesis reciprocally.     

Association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with advanced cancer

ContextPatients with advanced cancer often experience symptoms such as pain, anorexia, and fatigue. Opioid therapy for the management of cancer pain may result in neurohormonal dysfunction that may contribute to a patient’s symptom burden.ObjectivesTo examine the association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with cancer.MethodsA retrospective chart review was performed on 77 consecutive patients with advanced cancer referred for symptoms of fatigue or cachexia. We collected information regarding cortisol levels (am or random), testosterone levels (men only), morphine equivalent daily dose (MEDD), and symptom severity measured by the Edmonton Symptom Assessment Scale. Nonparametric correlation analysis was performed.ResultsThe median age was 63 years (range 24–79), and 62% were men (n = 48). Most patients had gastrointestinal (n = 33, 43%) or thoracic (n = 21, 27%) malignancies and were Caucasian (n = 46, 60%). The median random cortisol level was 19.1 μg/dL (Q1–Q3, 13.4–23.8 [normal, 4.3–22.4]), which correlated with MEDD (Spearman coefficient, 0.25, P = 0.032) and symptoms including pain (0.50, P < 0.001), fatigue (0.29, P = 0.012), nausea (0.34, P = 0.003), depression (0.24, P = 0.032), and anxiety (0.25, P = 0.031). Pain and nausea remained significant after Bonferroni correction. Median morning cortisol level (n = 28) was 20.6 μg/dL (Q1–Q3, 16.6–25.4) and significantly correlated with pain (0.55, P = 0.003) after Bonferroni correction. Patients with a MEDD <30 mg/day had a mean random cortisol level of 16.6 μg/dL, whereas patients with a MEDD ≥30 mg/day had a mean random cortisol level of 20.6 μg/dL (P = 0.01). In 44 male patients with cancer, MEDD was inversely correlated with the total testosterone level (?0.52, P = 0.001).ConclusionIn patients with advanced cancer, elevated random cortisol levels were associated with pain and opioid use, although abnormally low levels of cortisol were found to be infrequent. Patients on higher opioid therapy (MEDD >30) had increased cortisol levels, and male patients had lower testosterone levels. Our study suggests that opioid therapy in patients with advanced cancer may inhibit gonadal function while sparing the adrenal axis. Future studies are needed.     

The dermatan sulfate-dependent anticoagulant pathway is mostly preserved in aneurysm and in severe atherosclerotic lesions while the heparan sulfate pathway is disrupted

BackgroundThe pathogenesis of abdominal aortic aneurysm is associated with changes of several components of arterial wall. Vascular glycosaminoglycans contribute to the non-thrombogenic activity of blood vessels. We investigated whether modifications of glycosaminoglycans in human abdominal aortic aneurysm affect their anticoagulant properties.MethodsGlycosaminoglycans were extracted from abdominal aortic aneurysms (n = 11) derived from reconstitution surgeries, human abdominal aortas (n = 9) from normal organ transplant donors and from preserved (n = 10) and atherosclerotic (n = 17) segments obtained from autopsy of an old patient. Glycosaminoglycan composition, concentration and anticoagulant activity were determined.ResultsGlycosaminoglycans extracted from aneurysms have a more potent anticoagulant activity than those from normal arteries of young adults, mostly due to a relative enrichment of dermatan sulfate, which potentiates heparin cofactor II inhibition of thrombin. Arterial segments of aged patient with severe atherosclerosis showed a glycosaminoglycan composition similar to aneurysms samples. Glycosaminoglycans extracted from these regions showed also a more potent heparin cofactor II-dependent anticoagulant activity than lesion-free areas due to the relative enrichment of dermatan sulfate.ConclusionThe anticoagulant activity from abdominal aortic aneurysms is preserved. No modifications particular to the aneurysms were dissociated from those observed in atherosclerosis.     

Plasma ceruloplasmin as a biomarker for obesity: a proteomic approach

ObjectivesThis study aimed to investigate new biomarkers of obesity particularly in relation with inflammation-associated proteins using protein differential display techniques.Design and methodsComparison of protein expression in plasma between non-obese (n = 109, body mass index, BMI < 25 kg/m²) and obese (n = 32, BMI ≥ 25 kg/m²) groups was carried out using two-dimensional gel electrophoresis (2-DE) analysis. ELISA was also performed for validation.ResultsAmong six differentially expressed protein spots, ceruloplasmin (Cp) and fibrinogen were over-expressed in obese group. Plasma Cp levels were significantly higher in obese group than non-obese group (34.0 ± 8.6 vs. 41.3 ± 12.7 mg/dL, p < 0.001) and positively correlated with age (r = 0.253, p < 0.005), BMI (r = 0.265, p < 0.001) and hsCRP (r = 0.385, p < 0.001). In stepwise multiple linear regression analysis, plasma Cp along with hsCRP were found predictors for obesity (adjusted β-coefficient = 0.266, p < 0.01).ConclusionElevated plasma Cp levels were significantly associated with obesity, which may be suggested to be a marker of obesity.     

Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome

ObjectivesOur aim was to explore (i) the difference in concentration of IL-6, TNF-α and IL-10 between acute ischemic stroke patients and control individuals; (ii) the association of plasma cytokine concentration with stroke severity at admission assessed by NIHSS and stroke outcome in 90 days assessed by Barthel index (BI) and modified Rankin scale (mRS).Materials and methodsStudy included 68 stroke patients admitted within 12 h of symptoms onset and 71 controls.ResultsIL-6 was increased in patients relative to controls (P = 0.035) and this increase was associated with severe stroke (P = 0.007) and worse outcome (P = 0.030 and 0.019; assessed by BI and mRS, respectively), whereas IL-10 was decreased (P = 0.044) and associated with better outcome (P = 0.043). TNF-α did not differ between studied groups (P = 0.302).ConclusionsIncreased IL-6 and reduced IL-10 concentrations are present in early stroke period and are associated with a degree of neurological deficit and/or stroke outcome.