Phospholipid transfer protein activity is associated with inflammatory markers in patients with cardiovascular disease

Plasma phospholipid lipid transfer protein (PLTP) has several known key functions in lipoprotein metabolism. Recent studies suggest that it also may play a role in the inflammatory response. Inflammatory cell activity contributes to the development of atherosclerosis. To seek further evidence for the association of PLTP with inflammation, we studied the relationship between PLTP activity and five inflammatory markers [C-reactive protein (CRP), serum amyloid A (SAA), interleukin 6 (IL-6), white blood cells (WBC), and fibrinogen] in 93 patients with low HDL and cardiovascular disease (CVD). Plasma PLTP activity had the strongest correlation with CRP (r=0.332, P<0.001) followed by SAA (r=0.239, P=0.021). PLTP, CRP, and SAA were significantly associated with body mass index (BMI), insulin or glucose, apolipoprotein (apo) B, and/or apo E level (r=0.264-0.393, P<0.01). PLTP, SAA, and IL-6 also were associated with the concentration of HDL particles without apo A-II [Lp(A-I)](r=0.373-0.472, P<0.005, n=56), but not particles with apo A-II. Smoking was associated with increased PLTP activity, CRP, and WBC, and hypertension with increased PLTP activity. In linear models, CRP remained significantly associated with PLTP after adjustment of CVD risk factors and insulin resistance. Also, much of the variability of plasma PLTP activity was explained by CRP, BMI, Lp(A-I), smoking, glucose, and blood pressure. These findings show for the first time that plasma PLTP activity is associated positively with CRP in CVD, a state of chronic inflammation.     

Elevated circulating inflammatory markers in female patients with cardiac syndrome X

Background. The pathophysiological mechanism in cardiac syndrome X has been suggested as impairment in normal endothelial function of the coronary microvasculature, resulting in inadequate flow reserve. However, despite the extensive studies, the precise mechanisms in cardiac syndrome X remain unclear. Purpose. The present study was, therefore, to investigate whether inflammatory cells and markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) might be involved in the pathogenesis of cardiac syndrome X. Methods. Thirty-six female patients with cardiac syndrome X and 30 sex-matched normal controls were prospectively enrolled in this study. Blood samples were drawn for measuring white blood and monocyte cells, inflammatory markers such as CRP and IL-6, and data were compared between patients with cardiac syndrome X and normal controls. Results. The data showed that increased numbers of white blood and monocyte cells were found in patients with cardiac syndrome X compared with normal controls (white blood cells: 7072 ± 1146/mm³ vs. 6138 ± 1079/mm³; monocyte cells: 612 ± 186/mm³ vs. 539 ± 190/mm³ p < 0.05, respectively). Moreover, patients with cardiac syndrome X were detected to have significantly higher plasma CRP and IL-6 levels in comparison with patients with normal controls (CRP: 0.48 ± 0.26 mg/L vs. 0.22 ± 0.15 mg/L; IL-6: 13.4 ± 1.2 pg/dl vs. 6.2 ± 0.6 pg/dl, p < 0.01, respectively). The multivariate analysis showed that CRP was the independent variable most strongly associated with cardiac syndrome X. Conclusions. Our data suggested that low-grade, chronic inflammation might contribute to the development of cardiac syndrome X manifested by increased plasma levels of inflammatory cells and inflammatory markers.     

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.     

The potential of adipokines as therapeutic agents for cardiovascular disease

Adipose tissue functions as an endocrine organ by producing bioactive secretory proteins, also known as adipokines, that can directly act on nearby or remote organs. Most of the adipokines are upregulated by obese conditions, and typically promote obese complications. In contrast, some adipokines, such as adiponectin, CTRP9 and omentin, are downregulated in obese states. These factors exert salutary actions on obesity-linked cardiovascular disorders. In this review, we focus on the significance of adiponectin, CTRP9 and omentin as therapeutic agents for cardiovascular disease.     

T regulatory cells are markers of disease activity in multiple sclerosis patients

FoxP3⁺ Treg cells are believed to play a role in the occurrence of autoimmunity and in the determination of clinical recurrences. Contradictory reports are, however, available describing frequency and function of Treg cells during autoimmune diseases. We examined, by both polychromatic flow cytometry, and real-time RT-PCR, several Treg markers in peripheral blood mononuclear cells from patients with multiple sclerosis (MS), an autoimmune disease affecting the central nervous system. We found that Tregs, as defined by CD25, CD39, FoxP3, CTLA4, and GITR expression, were significantly decreased in stable MS patients as compared to healthy donors, but, surprisingly, restored to normal levels during an acute clinical attack. We conclude that Treg cells are not involved in causing clinical relapses, but rather react to inflammation in the attempt to restore homeostasis.     

Relationship among plasma adipokines, insulin and androgens level as well as biochemical glycemic and lipidemic markers with incidence of PCOS in women with normal BMI

Polycystic ovary syndrome (PCOS) is an endocrine disorder in women. Omentin-1 and vaspin are secretary adipokines that are produced by the visceral adipose tissue. These levels change in obese women with PCOS. The aim of this study is to investigate whether omentin and vaspin levels change in nonobese PCOS subjects. This study is a cross-sectional case control study in which 39 women with PCOS were picked out for this study. The inclusion criteria were based on the Rotterdam 2003 diagnostic criteria. The control group consisted of 39 women with normal pelvic sonographic reports having regular menstruation and showing no signs of infertility. The fasting plasma glucose (FPG), triglyceride (TG), Chol, and high-density lipoprotein cholesterol (HDL-C), insulin, testosterone, omentin and vaspin were measured by the enzymatic methods. The differences within these groups were calculated by the un-paired t-test and the Mann-Whitney test. The results from this study show a significant increase in the amount of insulin, testosterone, homeostasis model assessments for insulin resistance, TG and lower HDL in the patient group. No significant differences were seen in omentin, vaspin, FPG, Cho, low-density lipoprotein, very low-density lipoprotein cholesterol, blood urea nitrogen, Cr and homeostasis model assessments for B cell function levels between groups. Results show that PCOS is not a determinant of decreased omentin and vaspin plasma levels and those high androgen level and insulin resistances are warning signs of PCOS.     

Ghrelin gastrokinetic action in patients with neurogenic gastroparesis

Ghrelin has been shown to accelerate gastric emptying in animals where its effect appeared mediated through the vagus nerve. We aimed to verify the gastrokinetic capacity of ghrelin in human. Patients with gastroparesis attributed to a neural dysregulation by diabetes (n = 5) or surgical vagotomy (n = 1) were evaluated. The emptying of a test meal (420 kcal) was determined by the C13 octanoic acid breath test. Saline or synthetic ghrelin 1-4 microg/kg were given in 1 min bolus at the end of the meal. T-lag and T-1/2 were shorter during ghrelin than during saline administration [33 +/- 5 min versus 65 +/- 14 min (p < 0.01) and 119 +/- 6 min versus 173 +/- 38 min (p < 0.001)]. Ghrelin injection therefore accelerated gastric emptying of a meal in humans even in presence of a deficient gastric innervation.     

Genotoxic effects of radiotherapy and chemotherapy on circulating lymphocytes in patients with Hodgkin's disease

Chemical mutagenesis of Caenorhabditis elegans has relied primarily on EMS to produce missense mutations. The drawback of EMS mutagenesis is that the molecular lesions are primarily G/C --> A/T transitions. ENU has been shown to produce a different spectrum of mutations, but its greater toxicity to C. elegans makes it a difficult mutagen to use. We describe here methods for minimizing ENU toxicity in C. elegans. Methods include preparing ENU stocks in absolute ethanol and storing stock solutions for not more than 2 weeks at -20 degrees C. To maintain reasonable brood sizes of mutagenized animals, mutagenic solutions should not exceed 1.0mM ENU. We provide data which suggest ENU is degraded or altered to more toxic products in aqueous solution, but less so in solvents such as absolute ethanol.     

Snoring, inflammatory markers, adipokines and metabolic syndrome in apparently healthy Chinese

Objective

Chronic low-grade inflammation and adipokines dysregulation are linked to mechanisms underscoring the pathogenesis of obesity-related metabolic disorders. Little is known about roles of these cytokines on the association between snoring and metabolic syndrome (MetS). We aimed to investigate whether a cluster of cytokines are related to snoring frequency and its association with MetS in apparently healthy Chinese.

Methods

Current analyses used a population-based sample including 1059 Shanghai residents aged 35–54 years. Self-reported snoring frequency was classified as never, occasionally and regularly. Fasting plasma glucose, lipid profile, insulin, C-reactive protein, interleukin-6, interleukin-18, lipopolysaccharide binding protein, high-molecular-weight adiponectin and leptin were measured. MetS was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans.

Results

Overweight/obese subjects had significantly higher prevalence of regular snorers than their normal-weight counterparts (34.8% vs. 11.5%, P<0.001). Regular snoring was associated with unfavorable profile of inflammatory markers and adipokines. However, those associations were abolished after adjustment for body mass index (BMI) or waist circumference. The MetS risk (multivariate-adjusted odds ratio 5.41, 95% confidence interval 3.72–7.88) was substantially higher in regular snorers compared with non-snorers. Controlling for BMI remarkably attenuated the association (2.03, 1.26–3.26), while adjusting for inflammatory markers and adipokines showed little effects.

Conclusion

Frequent snoring was associated with an elevated MetS risk independent of lifestyle factors, adiposity, inflammatory markers and adipokines in apparently healthy Chinese. Whether snoring pattern is an economic and no-invasive indicator for screening high-risk persons needs to be addressed prospectively.     

Enhanced late-outgrowth circulating endothelial progenitor cell levels in rheumatoid arthritis and correlation with disease activity

Introduction  

Angiogenesis and vasculogenesis are critical in rheumatoid arthritis (RA) as they could be a key issue for chronic synovitis. Contradictory results have been published regarding circulating endothelial progenitor cells (EPCs) in RA. We herein investigated late outgrowth EPC sub-population using recent recommendations in patients with RA and healthy controls.     

Identification of canine circulating miRNAs as tumor biospecific markers using Next-Generation Sequencing and Q-RT-PCR

Delay in cancer diagnosis often results in metastasis and an inability to successfully treat the tumor. The use of broadly cancer-specific biomarkers at an early stage may improve cancer treatment and staging. This study has explored circulatory exosomal miRNAs as potential diagnostic biomarkers to identify cancer patients. Secretory exosomal miRNAs were isolated from 13 canine cancer cell lines (lymphoma, mast cell tumor, histiocytic cell line, osteosarcoma, melanoma, and breast tumor) and were sequenced by Next-Generation sequencing (NGS). We have identified 6 miRNAs (cfa-miR-9, -1841, ?1306, ?345, ?132, and ?26b) by NGS that were elevated in all cancer cell types. The miRNAs identified by NGS were then examined by Q-RT-PCR. The PCR data demonstrated similar expression patterns to those seen with NGS but provided fold differences that were much lower than those seen for NGS. Cfa-miR-9 was found to be the most consistently elevated miRNA in NGS and PCR, making it the most likely miRNA to prove diagnostic. In this study, we have demonstrated that it is possible to identify exosomal miRNAs with elevated secretion across multiple tumor types that could be used as circulatory diagnostic biomarkers for liquid biopsy in the future.     

Soluble tumour necrosis factor-alpha receptor I and interleukin-6 as markers of activity in thyrotoxic Graves' disease.

Autoimmune thyroid diseases are thought to be mediated by pro-inflammatory cytokines such as TNFalpha and IL-6. Serum levels of cytokines may indicate activity levels of immune functions. We investigated serum levels of IL-6 and of the soluble receptor of TNFalpha in patients with newly diagnosed onset of Graves' hyperthyroidism. The predominantly female group consisted of 39 patients, mean fT4 was 47.6 pg/ml (normal values 7.5=19.0 pg/ml). After diagnosis, all patients were treated with anti-thyroid drugs. Soluble Tumour Necrosis Factor Receptor I (TNF-RI) serum levels were found significantly increased (mean 3.7+/-1.3 ng/ml; p<0,01) compared to a matched group of apparent healthy individuals (mean sTNF-RI 1.8+/-0.5 ng/ml) and to a matched group of patients with treated Graves' disease (mean sTNF-RI 1.9+/-0.6 ng/ml). When IL-6 was assessed only 4 of the 39 patients exhibited increased serum levels. Our finding may indicate that sTNF-RI and possibly its ligand, TNFalpha, could play an important role in the onset of the acute stage of Graves' disease.     

Evaluation of neutrophil activity and circulating immune complexes levels in diabetic patients

We have studied chemiluminescence produced by neutrophils stimulated by opsonized zymosan in insulin dependent (IDD) and non insulin dependent (NIDD) diabetic patients. Chemiluminescence was evaluated as the integral and maximum peak, total time and time to maximum peak of the response curve to opsonized zymosan. These values were then compared with circulating immune complexes (CIC) and glucose levels. Both IDD and NIDD patients had significantly higher values of chemiluminescence and CIC than normal controls. We also observed that patients who had the highest values of CIC and chemiluminescence levels were the ones with clinical microvascular complications.     

Giant cell arteritis: immune and vascular aging as disease risk factors

Susceptibility for giant cell arteritis increases with chronological age, in parallel with age-related restructuring of the immune system and age-induced remodeling of the vascular wall. Immunosenescence results in shrinkage of the naïve T-cell pool, contraction of T-cell diversity, and impairment of innate immunity. Aging of immunocompetent cells forces the host to take alternative routes for protective immunity and confers risk for pathogenic immunity that causes chronic inflammatory tissue damage. Dwindling immunocompetence is particularly relevant as the aging host is forced to cope with an ever growing infectious load. Immunosenescence coincides with vascular aging during which the arterial wall undergoes dramatic structural changes and medium and large arteries lose their pliability and elasticity. On the molecular level, elastic fibers deteriorate and matrix proteins accumulate biochemical modifications. Thus, the aging process impacts the two major biologic systems that liaise to promote giant cell arteritis; the immune system and the vessel wall niche.     

Natriuretic peptides as prognostic and diagnostic markers in Chagas' disease

Atrial natriuretic factor (ANF) is a hormone secreted predominantly from atrial myocardium in response to changes in wall tension. Chagas' disease is caused by the parasite Trypanosom cruzi (T. cruzi), the heart being one of the most affected organs, resulting in myocarditis and chronic cardiomyopathy. The inflammatory response of the myocardium may be the result of factors such as ischemia, direct parasite invasion, and autoimmune mechanisms. In this review, we discuss the current knowledge about ANF in Chagas' disease and describe our findings in studying: (1) the development of chagasic cardiomyophathy in T. cruzi-infected rats and its relationship with plasma ANF levels; (2) the evolution of plasma ANF in chagasic patients in different stages (asymptomatic, with conduction defects and with chronic heart failure [CHF]); and (3) the possible usefulness of plasma ANF as a prognostic factor of development of myocardial compromise and survival. In rats, the elevated ANF levels found could mirror the inflammatory response of myocardial cells to acute T. cruzi infection and of progressive failure of cardiac function in the chronic infection. In patients, plasma ANF could be a sensitive marker capable of detecting gradual impairments in cardiac function and poor survival in CHF patients and of myocardiopathy development in the asymptomatic state.     

Inflammatory markers in chronic kidney disease and end stage renal disease patients

Molecular Biology Reports - Chronic kidney disease (CKD) is condition characterized by a gradual loss of kidney function, patient with CKD suffering from a variety of immune system defects. This...     

Oxidative stress as a potential biomarker for determining disease activity in patients with Rheumatoid Arthritis

Rheumatoid arthritis is an inflammatory, autoimmune disease where oxidative stress has been proposed to contribute to the joint tissue damage. To establish whether measurement of the redox status in blood mirrors the oxidant status at sites of inflammation in patients with rheumatoid arthritis, we concomitantly examined their oxidant status by spectrophotometry and/or flow cytometry. The basal levels of total reactive oxygen species (ROS), superoxide and hydroxyl radicals were significantly raised in neutrophils sourced from peripheral blood and synovial infiltrate, as also showed a strong positive correlation; however, there was no major increase in the reactive nitrogen species RNS generated in monocytes from both sources. Furthermore, raised levels of superoxide in neutrophils of synovial infiltrate showed a positive correlation with NADPH oxidase activity in synovial fluid. Additionally, as ROS generated in both peripheral blood and synovial infiltrate correlated positively with both DAS 28 and CRP/anti-CCP levels, its measurement can serve as an indirect measure of the degree of inflammation in patients with RA.