Association of brain-type natriuretic protein and cardiac troponin I with incipient cardiovascular disease in chimpanzees (Pan troglodytes)

Cardiovascular disease (CVD) is the primary cause of morbidity and mortality in chimpanzees, but its etiology and clinical presentations remain poorly understood. The disease in chimpanzees differs sufficiently from that in humans that simple extrapolation from human findings are inadequate to guide clinical diagnoses. Nevertheless, the burden of disease posed by CVD made it important to attempt to identify specific chimpanzees at risk of developing CVD to allow clinical intervention prior to clinical presentation of advanced disease. We screened 4 CVD biomarkers used in human and veterinary medicine to identify markers with prognostic value in chimpanzees. Biomarkers included complete lipid panel, C-reactive protein, brain-type natriuretic protein, and cardiac troponin I. Serum levels of brain-type natriuretic protein differed between chimpanzees with CVD and heart-healthy controls. Cardiac troponin I gave mixed results. C-reactive protein and lipid panel values were not informative for cardiovascular disease, although total cholesterol, LDL-cholesterol, and triglycerides increased significantly with decade of life. Values of braintype natriuretic protein exceeding 163 mg/mL had a specificity of 90.5% for CVD, whereas levels of cardiac troponin I above the threshold of detection (0.20 ng/mL) appeared to be clinically relevant. More extensive clinical studies are recommended to validate these specific values. We conclude that brain-type natriuretic protein and possibly cardiac troponin I are useful diagnostic biomarkers for incipient CVD processes in chimpanzees.     

Oral health status,C-reactive protein and mortality--a 10 year follow-up study

Background: Epidemiological studies have reported a strong association between C‐reactive protein (CRP) and cardiovascular diseases (CVD). Elevated CRP levels have been observed both in dentate individuals with chronic dental infections like periodontal disease and in those edentulous. The mechanisms behind these observations, especially the reasons for the elevation of CRP in the edentulous, are poorly understood. The comparative data on the importance of these inflammatory conditions in the oral cavity as causes of elevated CRP levels and CVD risk factors are also limited. Objective: To determine if edentulism is associated with increased levels of CRP and investigate the possible mechanism for this association; and to study the influence of periodontal disease and edentulism on 10‐year mortality. Subjects: Of the 364 subjects aged 76,81, and 86 years in 1990,196 were dentate and 168 edentulous. By December 1999, 179 had died, almost half (n=87) of them due to cardiovascular disease. Results: Significantly more of the edentulous subjects had elevated (>3 mg/L) CRP levels as compared to those with at least 20 teeth (p<0.01). They also had high salivary microbial counts (p<0.05), and more mucosal lesions (p<0.0001) than those with at least 20 teeth. In multivariate analysis, high microbial counts (OR 2.3, CI 1.06‐5.05) and mucosal lesions (OR 2.18, CI 1.03‐4.61) were significantly associated with elevated CRP levels. The risk for all‐cause mortality was non‐significantly elevated among the edentulous (RR 1.48, CI 0.95 – 2.31) and dentate with periodontal disease (RR 1.58, CI 0.96 – 2.61). CVD mortality was significantly higher among the dentate with periodontal disease (RR 1.97, CI 1.01 – 3.85) when compared with dentate without periodontal disease. Conclusion: Among the edentulous, chronic infections like denture‐related mucosal lesions are important determinants of elevated CRP, comparable to periodontal disease in the dentate. Elevated CRP per se and edentulism were not significantly associated with increased mortality. Periodontal disease was, however, still associated with a two‐fold CVD mortality in this very old population.     

Classical cardiovascular disease risk factors associate with vascular function and morphology in rheumatoid arthritis: a six-year prospective study

Introduction

Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD). An early manifestation of CVD is endothelial dysfunction which can lead to functional and morphological vascular abnormalities. Classical CVD risk factors and inflammation are both implicated in causing endothelial dysfunction in RA. The objective of the present study was to examine the effect of baseline inflammation, cumulative inflammation, and classical CVD risk factors on the vasculature following a six-year follow-up period.

Methods

A total of 201 RA patients (155 females, median age (25th to 75th percentile): 61 years (53 to 67)) were examined at baseline (2006) for presence of classical CVD risk factors and determination of inflammation using C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). At follow-up (2012) patients underwent assessments of microvascular and macrovascular endothelium-dependent and endothelium-independent function, along with assessment of carotid atherosclerosis. The CRP and ESR were recorded from the baseline study visit to the follow-up visit for each patient to calculate cumulative inflammatory burden.

Results

Classical CVD risk factors, but not RA disease-related inflammation, predicted microvascular endothelium-dependent and endothelium-independent function, macrovascular endothelium-independent function and carotid atherosclerosis. These findings were similar in a sub-group of patients free from CVD, and not receiving non-steroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors or biologics. Cumulative inflammation was not associated with microvascular and macrovascular endothelial function, but a weak association was apparent between area under the curve for CRP and carotid atherosclerosis.

Conclusions

Classical CVD risk factors may be better long-term predictors of vascular function and morphology than systemic disease-related inflammation in patients with RA. Further studies are needed to confirm if assessments of vascular function and morphology are predictive of long-term CV outcomes in RA.     

Inflammation but not oxidative stress is associated with beta-chemokine levels and prevalence of cardiovascular disease in uraemic patients

Inflammation and oxidative stress (SOX) have been reported in patients with chronic renal failure (CRF), but their influence on β-chemokines levels and cardiovascular disease (CVD) prevalence remains unknown. We assessed β-chemokines, SOX markers and high sensitivity C-reactive protein (hs CRP) as a marker of inflammation in 40 uraemic patients, both with as well as without CVD and 20 controls. Compared with the controls, the patients with CVD showed a significant increase in plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), total peroxide (both p < 0.05), macrophage inflammatory protein 1β (MIP-1β) and hs CRP (both p < 0.01). The values of MCP-1 and hs CRP were more elevated in patients with CVD than without CVD (p < 0.01 and p < 0.05; respectively). Both subgroup of CRF patients were lower of regulated upon activation, normal T cell expressed and secreted (RANTES) levels than in the controls (both p < 0.001). The positive relationships were between hs CRP and presence of CVD, MIP-1β (both p < 0.01) and MCP-1 levels (p < 0.05). SOX markers did not show any significant correlation with β-chemokines, hs CRP and presence of CVD. We documented that increased inflammation but not SOX were associated with significant elevation in plasma β-chemokines levels and CVD prevalence in CRF patients not requiring dialysis.     

Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor uptake

We recently reported that methionine-loaded human umbilical vein endothelial cells (HUVECs) exported homocysteine (Hcy) and were associated with hydroxyl radical generation and oxidation of lipids in LDL. Herein we have analysed the Hcy-induced posttranslational modifications (PTMs) of LDL protein. PTMs have been characterised using electrophoretic mobility shift, protein carbonyl ELISA, HPLC with electrochemical detection and Western blotting of 3-nitrotyrosine, and LDL uptake by scavenger receptors on monocyte/macrophages. We have also analysed PTMs in LDL isolated from rheumatoid (RA) and osteo-(OA) arthritis patients with cardiovascular disease (CVD). While reagent Hcy (< 50 microM) promoted copper-catalysed LDL protein oxidation, Hcy released from methionine-loaded HUVECs promoted LDL protein nitration. In addition, LDL nitration was associated with enhanced monocyte/macrophage uptake when compared with LDL oxidation. LDL protein nitration and uptake by monocytes, but not carbonyl formation, was elevated in both RA and OA patients with CVD compared with disease-matched patients that had no evidence of CVD. Moreover, a direct correlation between plasma total Hcy (tHcy) and LDL uptake was observed. The present studies suggest that elevated plasma tHcy may promote LDL nitration and increased scavenger receptor uptake, providing a molecular mechanism that may contribute to the clinical link between CVD and elevated plasma tHcy.     

Paradoxical Association of C-Reactive Protein with Endothelial Function in Rheumatoid Arthritis

Background

Within the general population, levels of C-reactive protein (CRP) are positively associated with atherosclerotic cardiovascular disease (CVD). Whether CRP is causally implicated in atherogenesis or is the results of atherosclerosis is disputed. A role of CRP to protect endothelium-derived nitric oxide (EDNO) has been suggested. We examined the association of CRP with EDNO-dependent vasomotor function and subclinical measures of atherosclerosis and arteriosclerosis in patients with raised CRP resulting from rheumatoid arthritis (RA).

Methodology/Principal Findings

Patients with RA (n = 59) and healthy control subjects (n = 123), underwent measures of high sensitivity CRP, flow-mediated dilation (FMD, dependent on EDNO), intima-media thickness (IMT, a measure of subclinical atherosclerosis) and aortic pulse wave velocity (PWV, a measure of arteriosclerosis). IMT and PWV were elevated in patients with RA compared to controls but FMD was similar in the two groups. In patients with RA, IMT and PWV were not correlated with CRP but FMD was positively independently correlated with CRP (P<0.01).

Conclusions/Significance

These findings argue against a causal role of CRP in atherogenesis and are consistent with a protective effect of CRP on EDNO bioavailability.     

C 反应蛋白检测在急性脑梗死患者中的临床应用价值分析

目的:探讨血清中C反应蛋白在急性脑梗死患者中的临床应用价值。方法:选择2010年4月至2011年4月间,我院收治的急性脑梗死(ACI)患者87例,以同时期的62名健康体检者为对照,分析ACI患者发病后1、3、7、14、28天血清C反应蛋白(CRP)水平与正常对照组的差别。以血清CRP≥12mg/L作为A组,CRP<12mg/L作为B组,分析两组的病情和预后。结果:ACI患者发病后血清CRP浓度随时间推移先升高后降低,在第3d时达到最大值;各时段均高于对照组(P>0.05);A组的病情严重程度高于B组,预后较B组差。结论:CRP在ACI患者血清中显著升高且呈动态性变化;血清CRP≥12mg/L者,病情较重、预后较差。     

BMI, waist circumference, and selected cardiovascular disease risk factors among preschool-age children

In adults, overweight is often associated with other cardiovascular disease (CVD) risk factors. We determined whether these associations were also present in young children. This study examined the relationships between elevated BMI (≥85th and ≥95th percentiles for age and sex) and the highest quintile of waist circumference (WC) with CVD risk factors, including fasting triglyceride (TGL), high- and low-density lipoprotein (HDL and LDL), total cholesterol (TC), non-HDL cholesterol, and C-reactive protein (CRP) in 3,644 3- to 6-year-old children included in the 1999-2008 National Health and Nutrition Examination Surveys (NHANES). Results showed that 20% (highest quintile) of the sample had a TC >170 mg/dl, LDL >109 mg/dl, TGL >103 mg/dl, non-HDL >128 mg/dl, CRP >0.13 mg/dl, WC >57.2 cm, and HDL <42 mg/dl. Increased BMI and WC were associated with increased CRP levels in non-Hispanic black boys and girls, Hispanic boys, and non-Hispanic white girls, whereas elevated TGL and non-HDL cholesterol and low HDL cholesterol were generally associated with elevated BMI and WC in Hispanic children. TC and LDL cholesterol were not significantly associated with elevated weight in 3- to 6-year-olds. BMI and WC were similar in predicting the same risk factors. In summary, this analysis shows that in preschool-age children, greater BMI and WC are associated with biomarkers that are related to CVD risk, but these associations vary by ethnicity. Child health providers should consider using both BMI and WC to identify young children who may be at risk for elevated CVD biomarkers.     

Lipid profiles and oxidative stress parameters in male and female hemodialysis patients

To study atherogenesis markers in patients with stage 5D chronic kidney disease (CKD-5D) on hemodialysis to determine which parameters are modified and whether their behavior differ between male and female patients of similar age. Total cholesterol, triglycerides, glucose, total proteins, HDL-cholesterol, LDL-cholesterol, oxidative modification of low-density lipoprotein-cholesterol, autoantibodies against oxidized low-density lipoproteins-cholesterol, homocysteine (Hcy), folate, and vitamin B12 were measured in male and female controls and CKD-5D patients on hemodialysis for >6 months. The CKD-5D patients had significantly lower cholesterol, LDL-c and ox-LDL levels and significantly higher ox-LDL-AB and Hcy levels versus their respective controls. The reduction in ox-LDL in CKD patients does not imply a lower risk of atherosclerosis. In fact, the risk may be higher due to a greater capture of ox-LDL by macrophage scavenger receptors, which are increased in these patients. Elevated Hcy levels may also be a risk factor for atherosclerosis in male and female CKD-5D patients.     

Matrix metalloproteinases MMP-3 and MMP-1 levels in sera and synovial fluids in patients with rheumatoid arthritis and osteoarthritis

OBJECTIVES: To investigate whether serum levels of matrix metalloproteinases (MMP-3, stromelysin) and (MMP-1, collagenase) are specifically elevated in joint disease as rheumatoid arthritis (RA) compared to osteoarthritis (OA), and to assess how these markers reflect the clinical activity of RA compared to circulating cytokine as tumor necrosis factor-alpha (TNF-alpha) as well as established variables as [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)]. SUBJECTS AND METHODS: This study included 22 patients with RA, 10 patients with OA and 10 healthy control subjects matched for age and sex. Patients with superimposed infection were excluded. Serum levels of MMP-3, MMP-1, TNF-alpha and CRP were assayed. Synovial fluid (SF) levels of MMP-3 and MMP-1 were also assayed. RESULTS: Serum levels of TNF-alpha and CRP in RA patients were significantly higher than normal subjects. Serum MMP-1 was significantly elevated in patients with RA and OA, compared to healthy controls but there were no significant differences between patients with RA and those with OA. Serum MMP-3 levels did not differ between OA patients and normal sera. However, RA patients displayed significantly elevated levels of this enzyme, compared to OA and control sera. Levels of MMP-3 and MMP-1 in the SF of RA patients were significantly higher than in OA fluids. CRP, ESR, TNF-alpha and MMP-3 correlated significantly with the swollen joint count. The strongest positive correlations existed between rheumatoid activity as assessed by the levels of CRP and circulating levels of MMP-3. Similar correlations between TNF-alpha concentration and CRP, MMP-1 and MMP-3 were observed in RA patients. Serum levels of MMP-3 correlated significantly with serum concentrations of MMP-1 in RA patients (r = 0.487, p < 0.05). There was close correlation between serum and SF concentrations of MMP-3 in RA patients (r = 0.619, p < 0.01). In the same patients there was highly significant correlation between SF concentrations of MMP-3 and MMP-1 (r = 0.732, p < 0.001). CONCLUSIONS: Our data suggested that elevated MMP-3 levels reflected disease activity of RA better than cytokine levels. However, MMP-3 levels do not exceed the association of CRP with clinical activity.     

NT-proBNP Best Predictor of Cardiovascular Events and Cardiovascular Mortality in Secondary Prevention in Very Old Age: The Leiden 85-Plus Study

Background

In the aging population cardiovascular disease (CVD) is highly prevalent. Identification of very old persons at high risk of recurrent CVD is difficult, since traditional risk markers loose predictive value with age.

Methods

In a population-based sample of 282 85-year old participants with established CVD from the Leiden 85-plus Study, we studied predictive values of traditional cardiovascular risk markers, a history of major CVD (myocardial infarction, stroke or arterial surgery), and new cardiovascular biomarkers (estimated glomerular filtration rate (MDRD), C-reactive protein (CRP), homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP)) regarding 5-year risk of recurrent cardiovascular events and mortality (composite endpoint).

Results

During complete 5-year follow-up 157 (56%) participants died. 109 (39%) had a cardiovascular event or died from cardiovascular causes. Individually related to the composite endpoint were: a history of major CVD (HR 1.5 (95%CI 1.03-2.3)), CRP (HR 1.3 (95%CI 1.03-1.5)), homocysteine (HR 1.4 (95%CI 1.2-2.6)) and NT-proBNP (HR 1.7 (95%CI 1.4-2.1)). A prediction model including all traditional risk markers yielded a C-statistic of 0.59 (95%CI 0.52-0.66). Of all five new markers only addition of NT-proBNP improved the C-statistic (0.67 (95%CI 0.61-0.74, p=0.023)). The categoryless net reclassification improvement for NT-proBNP was 39% (p=0.001), for a history of major CVD 27.2% (p=0.03) and for homocysteine 24.7% (p=0.04).

Conclusions

Among very old subjects with established CVD, NT-proBNP was the strongest risk marker for cardiovascular events and cardiovascular mortality. When estimating risk in secondary prevention in very old age, use of NT-proBNP should be considered.     

The combination of homocysteine and C-reactive protein predicts the outcomes of Chinese patients with Parkinson's disease and vascular parkinsonism

Background

The elevation of plasma homocysteine (Hcy) and C-reactive protein (CRP) has been correlated to an increased risk of Parkinson''s disease (PD) or vascular diseases. The association and clinical relevance of a combined assessment of Hcy and CRP levels in patients with PD and vascular parkinsonism (VP) are unknown.

Methodology/Principal Findings

We performed a cross-sectional study of 88 Chinese patients with PD and VP using a clinical interview and the measurement of plasma Hcy and CRP to determine if Hcy and CRP levels in patients may predict the outcomes of the motor status, non-motor symptoms (NMS), disease severity, and cognitive declines. Each patient''s NMS, cognitive deficit, disease severity, and motor status were assessed by the Nonmotor Symptoms Scale (NMSS), Mini-Mental State Examination (MMSE), the modified Hoehn and Yahr staging scale (H&Y), and the unified Parkinson''s disease rating scale part III (UPDRS III), respectively. We found that 100% of patients with PD and VP presented with NMS. The UPDRS III significantly correlated with CRP (P = 0.011) and NMSS (P = 0.042) in PD patients. The H&Y was also correlated with Hcy (P = 0.002), CRP (P = 0.000), and NMSS (P = 0.023) in PD patients. In VP patients, the UPDRS III and H&Y were not significantly associated with NMSS, Hcy, CRP, or MMSE. Strong correlations were observed between Hcy and NMSS as well as between CRP and NMSS in PD and VP.

Conclusions/Significance

Our findings support the hypothesis that Hcy and CRP play important roles in the pathogenesis of PD. The combination of Hcy and CRP may be used to assess the progression of PD and VP. Whether or not anti-inflammatory medication could be used in the management of PD and VP will produce an interesting topic for further research.     

外周血HCY、PLR及hs-CRP预测原发性高血压患者颈动脉粥样硬化的诊断效能

摘要 目的：通过临床回顾性研究分析外周血同型半胱氨酸（HCY）、血小板淋巴细胞比值（PLR）及C反应蛋白（hs-CRP）预测原发性高血压（PH）患者颈动脉粥样硬化（AS）的诊断效能。方法：通过病历系统查询,收集2019年1月至2020年1月于我科收治的PH患者167例,根据患者IMT检查结果分为非AS组及AS组,同期选择于我院体检的健康人群40例为对照组,采集PH患者入院24h内的空腹静脉血5 mL,采集对照组于查体时的空腹静脉血5 mL,采用免疫荧光法检测受检者hs-CRP水平,采用循环酶法检测受检者HCY水平,采用血细胞检测仪检测受检者血小板及淋巴细胞水平,计算血小板与淋巴细胞比值(PLR)。比较各组受检者血清HCY、PLR及hs-CRP水平,采用Pearson线性相关分析各因子水平变化的相关性。采用多因素Logistics回归分析PH患者病发AS的影响因素,采用ROC曲线分析HCY、PLR及hs-CRP在预测PH患者病发AS中的价值。分析外周血HCY、PLR及hs-CRP预测原发性高血压患者颈动脉粥样硬化的诊断效能。结果：PH组患者血清HCY、PLR及hs-CRP水平明显高于对照组,AS组患者HCY、PLR及hs-CRP水平明显高于非AS组（P＜0.05）。采用Pearson线性相关分析得知,HCY、PLR及hs-CRP与IMT均呈明显正相关（r分别为0.451、0.519、0.615,P均＜0.05或＜0.01）。采用多因素Logistics回归分析得知,HCY、PLR及hs-CRP是影响PF患者病发AS的危险因素（P均＜0.05）。ROC曲线分析得出,hs-CRP诊断PH患者病发AS的AUC为0.764,HCY诊断PH患者病发AS的AUC为0.659,PLR诊断PH患者病发AS的AUC为0.704, 三者联合诊断PH患者病发AS的AUC为0.895。结论：PH病发AS的患者血清HCY、PLR及hs-CRP水平呈明显高表达状态,且与IMT水平呈明显正相关,是PH患者病发AS的危险因素,三者在诊断PH患者病发AS方面具有一定价值,其中三者联合价值最高,可在临床中广泛应用。     

Assessment of Predictive Markers for Placental Inflammatory Response in Preterm Births

Placental inflammatory response (PIR) is associated with adverse neonatal outcomes such as sepsis, cerebral palsy, low birth weight, preterm birth, and neonatal mortality. However, there is an urgent need for noninvasive and sensitive biomarkers for prediction of PIR. In this study, we evaluated the clinical usefulness of maternal serum inflammatory markers for prediction of PIR in women with impending preterm birth. We conducted a retrospective cohort study of 483 patients who delivered preterm neonates. Serum levels of leukocyte differential counts, C-reactive protein (CRP), and neutrophil to lymphocyte ratio (NLR) were compared between women with no placental inflammation and women with PIR. The mean neutrophil counts, CRP levels, and NLR in both the patients with histologic chorioamnionitis (HCA) alone and those with HCA with funisitis were significantly higher than those in women with no placental inflammation. Compared to leukocyte subset or CRP, NLR in women with funisitis was significantly higher than in women with HCA alone and showed higher predictive accuracy, along with 71.4% sensitivity, 77.9% specificity, 80.7% positive predictive value, and 67.8% negative predictive value for prediction of PIR. On Kaplan-Meier survival analysis, women with both an elevated level of CRP and a high NLR had a shorter admission-to-delivery interval compared to women with either an elevated level of CRP or a high NLR alone. NLR may be a predictive marker of PIR and could be used as a cost-effective parameter for identifying women at risk of PIR.     

IL-6 gene variation is associated with IL-6 and C-reactive protein levels but not cardiovascular outcomes in the Cardiovascular Health Study

Interleukin-6 (IL-6) and C-reactive protein (CRP) levels increase with age and likely play a role in adverse health outcomes in older adults. The relationship between IL-6 gene tag single nucleotide polymorphisms (SNPs) and circulating IL-6 and CRP levels, cardiovascular disease (CVD) outcomes, and mortality in Caucasian (CA) and African American (AA) participants of the Cardiovascular Health Study (CHS) was evaluated using ANCOVA and Cox proportional hazards models. The minor allele of the promoter SNP 1510 and intronic SNP 3572 associates with significantly higher serum IL-6 and CRP levels in CA but not AA. The CRP association persisted after CA and AA populations were combined and after accounting for multiple comparisons. These associations did not carry through to cardiovascular disease outcomes. Decreased risk of stroke was identified in CA, with the minor allele of SNP 1111 (HRR 0.71, 95% CI 0.52, 0.95), P = 0.02, and increased risk of CVD and all-cause mortality (HRR 1.31, 95% CI 1.05–1.64) in AAs heterozygote for SNP 2989. While genetic variation in the IL-6 gene was associated with circulating IL-6 and especially with CRP concentrations in this study, there is little evidence for association between common IL-6 gene variation and adverse health outcomes in this population of older adults.     

The Relationship between Gene Polymorphism and CRP Level in a Chinese Han Population

We investigated the relationships among the +1444C/T polymorphism in the C-reactive protein (CRP) gene and the concentration of CRP and the risk of coronary heart disease. Using polymerase chain reaction-restriction fragment length polymorphism, we analyzed the frequency distribution of genotypes and alleles of the +1444C/T polymorphism in samples from 128 patients with coronary heart disease (coronary stenosis more than 50%) and 119 unrelated normal individuals. The plasma levels of CRP and lipids in the subjects were also measured. The frequencies of the genotypes were CC 89.1%, CT 10.9%, and TT 0% in patients and CC 89.9%, CT 10.1%, and TT 0% in controls. The frequency of allele C was 94.5% in patients and 95.0% in controls, and allele T was 5.5% in patients and 5.1% in controls. The distribution of genotypes and alleles in the Chinese Han population was significantly different from that of the Caucasian population. There were no significant differences between frequencies of genotype and allele of controls and those of patients (P>0.05), but in controls the concentrations of CRP in the CC genotype subgroup were significantly higher than those in the CT genotype subgroup (P<0.05). This suggests that the +1444C/T variant in the CRP gene influences the basal CRP level in normal people. These findings imply that there may eventually be a need to establish genotype-specific risk thresholds of the CRP level.     

Circulating beta-chemokines and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 system in hemodialyzed patients--role of oxidative stress

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), beta-chemokines, increased oxidative stress (SOX) and inflammation have been implicated as important factors in atherosclerosis and vascular remodeling. We hypothesized the possible roles of beta-chemokines [monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory proteins (MIP-1alpha, MIP-1beta) and regulated upon activation, normal T-cell expressed and secreted (RANTES)] as regulators of the metabolism of the vascular extracellular matrix in conditions of increased SOX in hemodialysis (HD) patients. We compared pre-dialysis levels of MMP-9/TIMP-1 system, beta-chemokines, Cu/Zn superoxide dismutase (Cu/Zn SOD) as a marker of SOX and C-reactive protein (CRP) as a marker of inflammation in HD patients with and without cardiovascular disease (CVD) to those of controls. HD patients, particularly those with CVD, showed a significant increase in values of Cu/Zn SOD, CRP, TIMP-1, TIMP-1/MMP-9 ratio, MCP-1 and MIP-1beta, whereas RANTES levels were lower than in the controls. The levels of MIP-1alpha as well as MMP-9 in all HD groups were similar to the controls. The positive correlations were observed between the MMP-9/TIMP-1 system and beta-chemokines, SOX and inflammation in whole HD group and in the subgroup with CVD. Multivariate analysis showed that the duration of dialysis followed by Cu/Zn SOD, MIP-1alpha and beta levels were the significant positive predictors of TIMP-1. In conclusion, our data show that MMP-9/TIMP-1 system and beta-chemokines could cooperate in conditions of elevated SOX, which ultimately predisposes hemodialysis patients to accelerated atherosclerosis.     

A multifaceted analysis of immune-endocrine-metabolic alterations in patients with pulmonary tuberculosis

Our study investigated the circulating levels of factors involved in immune-inflammatory-endocrine-metabolic responses in patients with tuberculosis with the aim of uncovering a relation between certain immune and hormonal patterns, their clinical status and in vitro immune response. The concentration of leptin, adiponectin, IL-6, IL-1β, ghrelin, C-reactive protein (CRP), cortisol and dehydroepiandrosterone (DHEA), and the in vitro immune response (lymphoproliferation and IFN-γ production) was evaluated in 53 patients with active untreated tuberculosis, 27 household contacts and 25 healthy controls, without significant age- or sex-related differences. Patients had a lower body mass index (BMI), reduced levels of leptin and DHEA, and increased concentrations of CRP, IL-6, cortisol, IL-1β and nearly significant adiponectin values than household contacts and controls. Within tuberculosis patients the BMI and leptin levels were positively correlated and decreased with increasing disease severity, whereas higher concentrations of IL-6, CRP, IL-1β, cortisol, and ghrelin were seen in cases with moderate to severe tuberculosis. Household contacts had lower DHEA and higher IL-6 levels than controls. Group classification by means of discriminant analysis and the k-nearest neighbor method showed that tuberculosis patients were clearly different from the other groups, having higher levels of CRP and lower DHEA concentration and BMI. Furthermore, plasma leptin levels were positively associated with the basal in vitro IFN-γ production and the ConA-driven proliferation of cells from tuberculosis patients. Present alterations in the communication between the neuro-endocrine and immune systems in tuberculosis may contribute to disease worsening.     

Systemic pentraxin-3 levels reflect vascular enhancement and progression in Takayasu arteritis

Introduction

Progression of arterial involvement is often observed in patients with Takayasu arteritis (TA) thought to be in remission. This reflects the failure of currently used biomarkers and activity criteria to detect smouldering inflammation occurring within arterial wall. Pentraxin-3 (PTX3) is a soluble pattern recognition receptor produced at sites of inflammation and could reveal systemic as well as localized inflammatory processes. We verified whether the blood concentrations of PTX3 and of C-reactive protein (CRP) in patients with Takayasu arteritis (TA) might reflect vascular wall involvement, as assessed by signal enhancement after contrast media administration, and the progression of arterial involvement.

Methods

A cross-sectional single-centre study was carried out on 42 patients with TA that comprised assessment of PTX3, of CRP and erythrocyte sedimentation velocity (ESR). In total, 20 healthy controls and 20 patients with Systemic Lupus Erythematous (SLE) served as controls. Vascular imaging was carried out by magnetic resonance angiography, doppler ultrasonography and computed tomography angiography.

Results

Patients with TA and SLE had higher plasmatic PTX3 and CRP concentrations than healthy controls (P = 0.009 and 0.017, respectively). PTX3 levels did not correlate with those of CRP. Patients with active systemic TA had significantly higher concentrations of CRP but similar levels of PTX3 than patients with quiescent disease. In contrast, patients with vascular inflammation detectable at imaging had higher PTX3 concentrations (P = 0.016) than those in which vessel inflammation was not evident, while CRP levels were similar. The concentration of PTX3 but not that of CRP was significantly higher in TA patients with worsening arterial lesions that were not receiving antagonists of tumor necrosis factor-α or interleukin-6.

Conclusions

Arterial inflammation and progression of vascular involvement influence plasma PTX3 levels in TA, while levels of CRP accurately reflect the burden of systemic inflammation. These results support the contention that PTX3 reflects different aspects of inflammation than CRP and might represent a biomarker of actual arteritis in TA.     

粪乳铁蛋白和C 反应蛋白对溃疡性结肠炎的评价

目的:研究粪乳铁蛋白(1actoferrin,LF)和C反应蛋白(C-reactive protein,CRP)对溃疡性结肠炎的严重程度、活动性和对治疗反应的评价作用。方法:选取我院2009-2010年43例特发性溃疡性结肠炎患者,同时进行对照平行研究。对患者进行临床评估、内镜和病理检查,了解疾病活动性、严重程度,并检测LF、CRP在治疗前后的水平。结果:与对照组相比较,病例组生物学标志都升高(P=0.000),特发性溃疡性结肠炎严重组粪LF和CRP更高,治疗后,生物学指标下降到与Mayo分数齐平,ROC曲线下面积分别为0.953和0.721,其灵敏度和特异性分别为:LF(90.7%,100%)和CRP(44.2%,100%)。结论:在对特发性溃疡性结肠炎的活动性、严重程度和对治疗反应的评价中,粪LF和CRP是非常有用的生物学指标。