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1.
Geschka S Kretschmer A Sharkovska Y Evgenov OV Lawrenz B Hucke A Hocher B Stasch JP 《PloS one》2011,6(7):e21853
Background
A direct pharmacological stimulation of soluble guanylate cyclase (sGC) is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521), have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO) and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension.Methods and Results
Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d) for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1.Conclusions
Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions. 相似文献2.
Objective
To evaluate the risk of cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids.Methods
Retrospective analysis of exposure to glucocorticoids in a prospective cohort of 353 patients with rheumatoid arthritis followed from June 2001 up to November 2011 for incident cardiovascular disease in a hospital-based outpatient cohort in the Netherlands. Hazard ratios with 95%-confidence intervals were calculated for the association between different types of exposure to glucocorticoids and incident cardiovascular disease. Associations were adjusted for demographics, cardiovascular risk factors and disease related parameters.Results
Recent and current exposure to glucocorticoids were associated with incident cardiovascular disease, as was a longer duration of exposure and cumulative exposure to glucocorticoids. Adjustment for disease activity and severity negated the association.Conclusion
In observational studies the finding of incident cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids is strongly confounded by indication due to high disease activity. The adverse cardiovascular effects of glucocorticoids might be balanced by positive effects working through inflammation control. 相似文献3.
Ruan Kruger Rudolph Schutte Hugo W. Huisman Peter Hindersson Michael H. Olsen Jesper Eugen-Olsen Aletta E. Schutte 《PloS one》2013,8(3)
Objective and design
This cross-sectional study aimed to investigate associations between a marker of cardiac strain, the N-terminal prohormone B-type natriuretic peptide (NT-proBNP), and inflammation as reflected by either a conventional or novel inflammatory marker in a bi-ethnic South African cohort.Methods and subjects
We measured NT-proBNP, C-reactive protein (CRP) and plasma-soluble urokinase plasminogen activator receptor (suPAR) levels along with conventional biomarkers in black (n = 117) and white (n = 116) men.Results
NT-proBNP, CRP and suPAR levels were higher in black compared to white men. NT-proBNP was significantly associated with both CRP (r = 0.38; p = 0.001) and suPAR (r = 0.42; p<0.001) in black men only. After full adjustment in multiple regression analyses, the above associations of NT-proBNP with CRP (β = 0.199; p = 0.018) and suPAR (β = 0.257; p<0.01) were confirmed in black men.Conclusion
These results suggest that a low-grade inflammatory state as reflected by both a conventional and novel marker of inflammation may contribute to higher cardiovascular risk as reflected by the associations obtained with a marker of cardiac strain in black South African men. 相似文献4.
Purpose
To describe women’s condom use and assess predictors of consistent condom use and dual method use in the 6 months after the initiation of oral contraception (OC).Methods
We conducted a planned secondary cohort analysis among women less than 25 years of age initiating oral contraceptives at public family planning clinics in Atlanta, Dallas and New York City, USA, as part of a randomized trial. These clinics provide care to predominantly African American or Hispanic women of low socioeconomic status. Participants completed interviews at enrollment and at 6 months after OC start. We used multivariate logistic regression to assess factors associated with consistent condom and dual method use at 6 months.Results
1281 participants met the inclusion criteria for this analysis. At enrollment prior to OC start, 28% were consistent condom users. In the six months after initiation of oral contraception, only 14% always used a condom and 4% always used dual methods. In multivariate analysis, receiving basic advice to always use a condom after OC initiation from a provider during the baseline clinic consultation was associated with a 50% increase in the odds of using condoms consistently. Only 28% of participants were given this condom use advice.Conclusions
This study documents a decline in women’s condom consistent use subsequent to initiation of the oral contraceptive and suggests that opportunities for positive intervention around condom use among women starting hormonal methods are being missed. Basic condom use advice, which is neither time consuming nor resource dependent, was associated with increased consistent use and should be immediately implemented in all family planning services. 相似文献5.
Yende S D'Angelo G Mayr F Kellum JA Weissfeld L Kaynar AM Young T Irani K Angus DC;GenIMS Investigators 《PloS one》2011,6(8):e22847
Background
Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes.Methods
In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality.Results
Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses).Conclusions
Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. 相似文献6.
Background
Because of its propensity to sequester in the placental intervillous space, Plasmodium falciparum can evade detection by peripheral smear in women with placental malaria (PM). We evaluated host biomarkers as potential indicators of occult PM infections.Methods and Findings
Using a case-control design, we evaluated the ability of biomarkers to identify PM in the absence of circulating peripheral parasites (n = 24) compared to placental smear-negative controls (n = 326). We measured levels of biomarkers (C3a, C5a, CRP, angiopoietin-1, angiopoietin-2, sTie-2, sEndoglin, VEGF, sFlt-1, tissue factor, and leptin) in maternal peripheral plasma at delivery. Using ROC curve analysis, we assessed the ability of clinical parameters and biomarkers to accurately detect PM infections identified by placental smear. We show that decreases in sFlt-1 and leptin and increases in CRP were associated with occult PM infections (p<0.01) and correlated with placental parasitaemia (p<0.01). Individually, all markers had moderate ability to diagnose occult PM infections with areas under the ROC between 0.62 and 0.72. In order to improve diagnostic performance, we generated simple scoring systems to identify PM infections using either a clinical score (0–2), a biomarker score (0–3) or a clinical plus biomarker score (0–5). The combinatorial model that incorporated both clinical parameters and biomarkers had an area under curve (AUC) of 0.85 (95% CI, 0.81-0.89), which was significantly better at identifying occult PM infections than the clinical score alone (p = 0.001).Conclusion
These data suggest that host biomarkers in the maternal peripheral blood may improve the detection of PM in the absence of peripheral parasitaemia. 相似文献7.
Background
Epidemiologic studies indirectly suggest that air pollution accelerates atherosclerosis. We hypothesized that individual exposure to particulate matter (PM) derived from fossil fuel would correlate with plasma concentrations of oxidized low-density lipoprotein (LDL), taken as a marker of atherosclerosis. We tested this hypothesis in patients with diabetes, who are at high risk for atherosclerosis.Methodology/Principal Findings
In a cross-sectional study of non-smoking adult outpatients with diabetes we assessed individual chronic exposure to PM by measuring the area occupied by carbon in airway macrophages, collected by sputum induction and by determining the distance from the patient''s residence to a major road, through geocoding. These exposure indices were regressed against plasma concentrations of oxidized LDL, von Willebrand factor and plasminogen activator inhibitor 1 (PAI-1). We could assess the carbon load of airway macrophages in 79 subjects (58 percent). Each doubling in the distance of residence from major roads was associated with a 0.027 µm2 decrease (95% confidence interval (CI): −0.048 to −0.0051) in the carbon load of airway macrophages. Independently from other covariates, we found that each increase of 0.25 µm2 [interquartile range (IQR)] in carbon load was associated with an increase of 7.3 U/L (95% CI: 1.3 to 13.3) in plasma oxidized LDL. Each doubling in distance of residence from major roads was associated with a decrease of −2.9 U/L (95% CI: −5.2 to −0.72) in oxidized LDL. Neither the carbon load of macrophages nor the distance from residence to major roads, were associated with plasma von Willebrand factor or PAI-1.Conclusions
The observed positive association, in a susceptible group of the general population, between plasma oxidized LDL levels and either the carbon load of airway macrophages or the proximity of the subject''s residence to busy roads suggests a proatherogenic effect of traffic air pollution. 相似文献8.
Kyong-Hui Lee Hye-Jung Jung Dong-Uk Park Seung-Hun Ryu Boowook Kim Kwon-Chul Ha Seungwon Kim Gwangyong Yi Chungsik Yoon 《PloS one》2015,10(8)
Objective
The purposes of this study were to determine the following: 1) the exposure levels of municipal household waste (MHW) workers to diesel particulate matter (DPM) using elemental carbon (EC), organic carbon (OC), total carbon (TC), black carbon (BC), and fine particulate matter (PM 2.5) as indicators; 2) the correlations among the indicators; 3) the optimal indicator for DPM; and 4) factors that influence personal exposure to DPM.Methods
A total of 72 workers in five MHW collection companies were assessed over a period of 7 days from June to September 2014. Respirable EC/OC samples were quantified using the thermal optical transmittance method. BC and PM 2.5 were measured using real-time monitors, an aethalometer and a laser photometer. All results were statistically analyzed for occupational and environmental variables to identify the exposure determinants of DPM.Results
The geometric mean of EC, OC, TC, BC and PM 2.5 concentrations were 4.8, 39.6, 44.8, 9.1 and 62.0 μg/m3, respectively. EC concentrations were significantly correlated with the concentrations of OC, TC and BC, but not with those of PM 2.5. The exposures of the MHW collectors to EC, OC, and TC were higher than those of the drivers (p<0.05). Workers of trucks meeting Euro 3 emission standard had higher exposures to EC, OC, TC and PM 2.5 than those working on Euro 4 trucks (p<0.05). Multiple regression analysis revealed that the job task, European engine emission standard, and average driving speed were the most influential factors in determining worker exposure.Conclusions
We assessed MHW workers’ exposure to DPM using parallel sampling of five possible indicators. Of these five indicators, EC was shown to be the most useful indicator of DPM exposure for MHW workers, and the job task, European emission standard, and average driving speed were the main determinants of EC exposure. 相似文献9.
Jinhua Wang Ashok Sharma Sharad A. Ghamande Stephen Bush Daron Ferris Wenbo Zhi Mingfang He Meiyao Wang Xiaoxiao Wang Eric Miller Diane Hopkins Michael Macfee Ruili Guan Jinhai Tang Jin-Xiong She 《PloS one》2013,8(11)
Background
Biomarkers play critical roles in early detection, diagnosis and monitoring of therapeutic outcome and recurrence of cancer. Previous biomarker research on ovarian cancer (OC) has mostly focused on the discovery and validation of diagnostic biomarkers. The primary purpose of this study is to identify serum biomarkers for prognosis and therapeutic outcomes of ovarian cancer.Experimental Design
Forty serum proteins were analyzed in 70 serum samples from healthy controls (HC) and 101 serum samples from serous OC patients at three different disease phases: post diagnosis (PD), remission (RM) and recurrence (RC). The utility of serum proteins as OC biomarkers was evaluated using a variety of statistical methods including survival analysis.Results
Ten serum proteins (PDGF-AB/BB, PDGF-AA, CRP, sFas, CA125, SAA, sTNFRII, sIL-6R, IGFBP6 and MDC) have individually good area-under-the-curve (AUC) values (AUC = 0.69–0.86) and more than 10 three-marker combinations have excellent AUC values (0.91–0.93) in distinguishing active cancer samples (PD & RC) from HC. The mean serum protein levels for RM samples are usually intermediate between HC and OC patients with active cancer (PD & RC). Most importantly, five proteins (sICAM1, RANTES, sgp130, sTNFR-II and sVCAM1) measured at remission can classify, individually and in combination, serous OC patients into two subsets with significantly different overall survival (best HR = 17, p<10−3).Conclusion
We identified five serum proteins which, when measured at remission, can accurately predict the overall survival of serous OC patients, suggesting that they may be useful for monitoring the therapeutic outcomes for ovarian cancer. 相似文献10.
Stephanie L. Harrison Jie Ding Eugene Y. H. Tang Mario Siervo Louise Robinson Carol Jagger Blossom C. M. Stephan 《PloS one》2014,9(12)
Background
Cardiovascular disease and its risk factors have consistently been associated with poor cognitive function and incident dementia. Whether cardiovascular disease prediction models, developed to predict an individual''s risk of future cardiovascular disease or stroke, are also informative for predicting risk of cognitive decline and dementia is not known.Objective
The objective of this systematic review was to compare cohort studies examining the association between cardiovascular disease risk models and longitudinal changes in cognitive function or risk of incident cognitive impairment or dementia.Materials and Methods
Medline, PsychINFO, and Embase were searched from inception to March 28, 2014. From 3,413 records initially screened, 21 were included.Results
The association between numerous different cardiovascular disease risk models and cognitive outcomes has been tested, including Framingham and non-Framingham risk models. Five studies examined dementia as an outcome; fourteen studies examined cognitive decline or incident cognitive impairment as an outcome; and two studies examined both dementia and cognitive changes as outcomes. In all studies, higher cardiovascular disease risk scores were associated with cognitive changes or risk of dementia. Only four studies reported model prognostic performance indices, such as Area Under the Curve (AUC), for predicting incident dementia or cognitive impairment and these studies all examined non-Framingham Risk models (AUC range: 0.74 to 0.78).Conclusions
Cardiovascular risk prediction models are associated with cognitive changes over time and risk of dementia. Such models are easily obtainable in clinical and research settings and may be useful for identifying individuals at high risk of future cognitive decline and dementia. 相似文献11.
Vincent Daien Isabelle Carriere Ryo Kawasaki Jean-Paul Cristol Max Villain Pierre Fesler Karen Ritchie Cecile Delcourt 《PloS one》2013,8(7)
Purpose
Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology.Patients and Methods
Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3) activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP) and orosomucoid.Results
In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (p = 0.003) whereas larger venular caliber was associated with higher levels of hsCRP (p = 0.0001) and orosomucoid (p = 0.01).Conclusion
In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology. 相似文献12.
Michael Centola Guy Cavet Yijing Shen Saroja Ramanujan Nicholas Knowlton Kathryn A. Swan Mary Turner Chris Sutton Dustin R. Smith Douglas J. Haney David Chernoff Lyndal K. Hesterberg John P. Carulli Peter C. Taylor Nancy A. Shadick Michael E. Weinblatt Jeffrey R. Curtis 《PloS one》2013,8(4)
Background
Disease activity measurement is a key component of rheumatoid arthritis (RA) management. Biomarkers that capture the complex and heterogeneous biology of RA have the potential to complement clinical disease activity assessment.Objectives
To develop a multi-biomarker disease activity (MBDA) test for rheumatoid arthritis.Methods
Candidate serum protein biomarkers were selected from extensive literature screens, bioinformatics databases, mRNA expression and protein microarray data. Quantitative assays were identified and optimized for measuring candidate biomarkers in RA patient sera. Biomarkers with qualifying assays were prioritized in a series of studies based on their correlations to RA clinical disease activity (e.g. the Disease Activity Score 28-C-Reactive Protein [DAS28-CRP], a validated metric commonly used in clinical trials) and their contributions to multivariate models. Prioritized biomarkers were used to train an algorithm to measure disease activity, assessed by correlation to DAS and area under the receiver operating characteristic curve for classification of low vs. moderate/high disease activity. The effect of comorbidities on the MBDA score was evaluated using linear models with adjustment for multiple hypothesis testing.Results
130 candidate biomarkers were tested in feasibility studies and 25 were selected for algorithm training. Multi-biomarker statistical models outperformed individual biomarkers at estimating disease activity. Biomarker-based scores were significantly correlated with DAS28-CRP and could discriminate patients with low vs. moderate/high clinical disease activity. Such scores were also able to track changes in DAS28-CRP and were significantly associated with both joint inflammation measured by ultrasound and damage progression measured by radiography. The final MBDA algorithm uses 12 biomarkers to generate an MBDA score between 1 and 100. No significant effects on the MBDA score were found for common comorbidities.Conclusion
We followed a stepwise approach to develop a quantitative serum-based measure of RA disease activity, based on 12-biomarkers, which was consistently associated with clinical disease activity levels. 相似文献13.
Adriana Rojas-Villarraga July-Vianneth Torres-Gonzalez ángela-María Ruiz-Sternberg 《PloS one》2014,9(8)
Background
There is conflicting data regarding exogenous sex hormones [oral contraceptives (OC) and hormonal replacement therapy (HRT)] exposure and different outcomes on Systemic Lupus Erythematosus (SLE). The aim of this work is to determine, through a systematic review and meta-analysis the risks associated with estrogen use for women with SLE as well as the association of estrogen with developing SLE.Methods and Findings
MEDLINE, EMBASE, SciElo, BIREME and the Cochrane library (1982 to July 2012), were databases from which were selected and reviewed (PRISMA guidelines) randomized controlled trials, cross-sectional, case-control and prospective or retrospective nonrandomized, comparative studies without language restrictions. Those were evaluated by two investigators who extracted information on study characteristics, outcomes of interest, risk of bias and summarized strength of evidence. A total of 6,879 articles were identified; 20 full-text articles were included. Thirty-two meta-analyses were developed. A significant association between HRT exposure (Random model) and an increased risk of developing SLE was found (Rate Ratio: 1.96; 95%-CI: 1.51–2.56; P-value<0.001). One of eleven meta-analyses evaluating the risk for SLE associated with OC exposure had a marginally significant result. There were no associations between HRT or OC exposure and specific outcomes of SLE. It was not always possible to Meta-analyze all the available data. There was a wide heterogeneity of SLE outcome measurements and estrogen therapy administration.Conclusion
An association between HRT exposure and SLE causality was observed. No association was found when analyzing the risk for SLE among OC users, however since women with high disease activity/Thromboses or antiphospholipid-antibodies were excluded from most of the studies, caution should be exercised in interpreting the present results. To identify risk factors that predispose healthy individuals to the development of SLE who are planning to start HRT or OC is suggested. 相似文献14.
Peter Willeit Alexander Thompson Thor Aspelund Ann Rumley Gudny Eiriksdottir Gordon Lowe Vilmundur Gudnason Emanuele Di Angelantonio 《PloS one》2013,8(2)
Background
Activation of blood coagulation and fibrinolysis may be associated with increased risk of coronary heart disease. We aimed to assess associations of circulating tissue plasminogen activator (t-PA) antigen, D-dimer and von Willebrand factor (VWF) with coronary heart disease risk.Design
Prospective case-control study, systematic review and meta-analyses.Methods
Measurements were made in 1925 people who had a first-ever nonfatal myocardial infarction or died of coronary heart disease during follow-up (median 19.4 years) and in 3616 controls nested within the prospective population-based Reykjavik Study.Results
Age and sex-adjusted odds ratios for coronary heart disease per 1 standard deviation higher baseline level were 1.25 (1.18, 1.33) for t-PA antigen, 1.01 (0.95, 1.07) for D-dimer and 1.11 (1.05, 1.18) for VWF. After additional adjustment for conventional cardiovascular risk factors, corresponding odds ratios were 1.07 (0.99, 1.14) for t-PA antigen, 1.06 (1.00, 1.13) for D-dimer and 1.08 (1.02, 1.15) for VWF. When combined with the results from previous prospective studies in a random-effects meta-analysis, overall adjusted odds ratios were 1.13 (1.06, 1.21) for t-PA antigen (13 studies, 5494 cases), 1.23 (1.16, 1.32) with D-dimer (18 studies, 6799 cases) and 1.16 (1.10, 1.22) with VWF (15 studies, 6556 cases).Conclusions
Concentrations of t-PA antigen, D-dimer and VWF may be more modestly associated with first-ever CHD events than previously reported. More detailed analysis is required to clarify whether these markers are causal risk factors or simply correlates of coronary heart disease. 相似文献15.
Matthieu Legrand Benedetta De Berardinis Hanna K. Gaggin Laura Magrini Arianna Belcher Benedetta Zancla Alexandra Femia Mandy Simon Shweta Motiwala Rasika Sambhare Salvatore Di Somma Alexandre Mebazaa Vishal S. Vaidya James L. Januzzi Jr from the Global Research on Acute Conditions Team 《PloS one》2014,9(11)
Objective
The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF).Methods
In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF.Results
26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF.Conclusions
In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153). 相似文献16.
Kenji Unno Masanori Ono Abigail D. Winder Kruti P. Maniar Ajit S. Paintal Yanni Yu Jian-Jun Wei John R. Lurain J. Julie Kim 《PloS one》2014,9(12)
Objective
Most endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis.Methods
Endometrial tumor tissue fragments (1.5 mm×1.5 mm) from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6–8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers.Results
Four cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor.Conclusion
Endometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer. 相似文献17.
Objective
To determine whether exposure to environmental tobacco smoke was associated with oxidative stress among patients hospitalised for acute myocardial infarction.Design
An existing cohort study of 1,261 patients hospitalised for acute myocardial infarction.Setting
Nine acute hospitals in Scotland.Participants
Sixty never smokers who had been exposed to environmental tobacco smoke (admission serum cotinine ≥3.0 ng/mL) were compared with 60 never smokers who had not (admission serum cotinine ≤0.1 ng/mL).Intervention
None.Main outcome measures
Three biomarkers of oxidative stress (protein carbonyl, malondialdehyde (MDA) and oxidised low-density lipoprotein (ox-LDL)) were measured on admission blood samples and adjusted for potential confounders.Results
After adjusting for baseline differences in age, sex and socioeconomic status, exposure to environmental tobacco smoke was associated with serum concentrations of both protein carbonyl (beta coefficient 7.96, 95% CI 0.76, 15.17, p = 0.031) and MDA (beta coefficient 10.57, 95% CI 4.32, 16.81, p = 0.001) but not ox-LDL (beta coefficient 2.14, 95% CI −8.94, 13.21, p = 0.703).Conclusions
Exposure to environmental tobacco smoke was associated with increased oxidative stress. Further studies are requires to explore the role of oxidative stress in the association between environmental tobacco smoke and myocardial infarction. 相似文献18.
Luis Bujanda Cristina Sarasqueta Angel Cosme Elizabeth Hijona José M. Enríquez-Navascués Carlos Placer Eloisa Villarreal Marta Herreros-Villanueva María D. Giraldez Meritxell Gironella Francesc Balaguer Antoni Castells 《PloS one》2013,8(1)
Background
Colorectal cancer (CRC) is the second most common cause of death from cancer in both men and women in the majority of developed countries. Molecular tests of blood could potentially provide this ideal screening tool.Aim
Our objective was to assess the usefulness of serum markers and mRNA expression levels in the diagnosis of CRC.Methods
In a prospective study, we measured mRNA expression levels of 13 markers (carbonic anhydrase, guanylyl cyclase C, plasminogen activator inhibitor, matrix metalloproteinase 7 (MMP7), urokinase-type plasminogen activator receptor (uPAR), urokinase-type plasminogen activator, survivin, tetranectin, vascular endothelial growth factor (VEGF), cytokeratin 20, thymidylate synthase, cyclooxygenase 2 (COX-2), and CD44) and three proteins in serum (alpha 1 antitrypsin, carcinoembryonic antigen (CEA) and activated C3 in 42 patients with CRC and 33 with normal colonoscopy results.Results
Alpha 1-antitrypsin was the serum marker that was most useful for CRC diagnosis (1.79±0.25 in the CRC group vs 1.27±0.25 in the control group, P<0.0005). The area under the ROC curve for alpha 1-antitrypsin was 0.88 (0.79–0.96). The mRNA expression levels of five markers were statistically different between CRC cases and controls: those for which the ROC area was over 75% were MMP7 (0.81) and tetranectin (0.80), COX-2 (0.78), uPAR (0.78) and carbonic anhydrase (0.77). The markers which identified early stage CRC (Stages I and II) were alpha 1-antitrypsin, uPAR, COX-2 and MMP7.Conclusions
Serum alpha 1-antitrypsin and the levels of mRNA expression of MMP7, COX-2 and uPAR have good diagnostic accuracy for CRC, even in the early stages. 相似文献19.
Boudjeltia KZ Faraut B Esposito MJ Stenuit P Dyzma M Antwerpen PV Brohée D Vanhamme L Moguilevsky N Vanhaeverbeek M Kerkhofs M 《PloS one》2011,6(11):e28230
Objectives
Many studies have evaluated the ways in which sleep disturbances may influence inflammation and the possible links of this effect to cardiovascular risk. Our objective was to investigate the effects of chronic sleep restriction and recovery on several blood cardiovascular biomarkers.Methods and Results
Nine healthy male non-smokers, aged 22–29 years, were admitted to the Sleep Laboratory for 11 days and nights under continuous electroencephalogram polysomnography. The study consisted of three baseline nights of 8 hours sleep (from 11 pm to 7 am), five sleep-restricted nights, during which sleep was allowed only between 1 am and 6 am, and three recovery nights of 8 hours sleep (11 pm to 7 am). Myeloperoxidase-modified low-density lipoprotein levels increased during the sleep-restricted period indicating an oxidative stress. A significant increase in the quantity of slow-wave sleep was measured during the first recovery night. After this first recovery night, insulin-like growth factor-1 levels increased and myeloperoxidase concentration peaked.Conclusions
We observed for the first time that sleep restriction and the recovery process are associated with differential changes in blood biomarkers of cardiovascular disease. 相似文献20.
Thijs C. van Holten Leonie F. Waanders Philip G. de Groot Joost Vissers Imo E. Hoefer Gerard Pasterkamp Menno W. J. Prins Mark Roest 《PloS one》2013,8(4)