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Systemic Levels (systemic + level)
Selected AbstractsComparison of the Systemic Levels of Inflammatory Markers after Percutaneous Coronary Intervention with Bare Metal versus Sirolimus-Eluting StentsJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2009ABDALLAH G. REBEIZ M.D., F.A.C.C. Background: Percutaneous coronary intervention (PCI) with bare metal stent (BMS) deployment causes plaque disruption and a rise in systemic levels of C-reactive protein (CRP), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. Our aim is to study whether PCI with sirolimus-eluting stent (SES) use attenuates this response. Methods: Patients with stable angina undergoing single-vessel PCI were enrolled in a randomized, open-label fashion into a BMS group or an SES group. Blood samples were drawn pre-PCI, 24 hours post-PCI, and 30 days post-PCI. Systemic concentrations of CRP, IL-6, and MCP-1 were measured at all time points. Results: In total, 41 patients were enrolled (21 in the BMS group and 20 in the SES group). The baseline plasma concentrations of all markers were comparable between groups. At 24 hours, the mean plasma CRP concentration in the SES group was 20.21 mg/dL versus 8.95 mg/dL in the BMS group (P = 0.15). The mean plasma IL-6 concentration at 24 hours was 25.41 pg/mL in the SES group versus 17.44 pg/mL in the BMS group (P = 0.17). The mean plasma MCP-1 concentration at 24 hours was 382.38 pg/mL in the SES group versus 329.04 pg/mL in the BMS group (P = 0.2). At 30 days, plasma concentrations of all three markers decreased to similar values between groups. Conclusions: The use of SES did not inhibit the rise in systemic concentrations of CRP, IL-6, and MCP-1 at 24 hours or 30 days post-PCI, compared with BMS. Moreover, at 24 hours, there was a trend for higher systemic levels of all proinflammatory markers in the SES group compared with the BMS cohort. [source] Systemic concentrations of antioxidants and biomarkers of macromolecular oxidative damage in horses with grass sicknessEQUINE VETERINARY JOURNAL, Issue 2 2003B. C. McGORUM Summary Reasons for performing study: The aetiopathogenesis of equine grass sickness (EGS) is unknown. The role of free radical-mediated neuronal damage has not previously been investigated in this condition. Objectives: To investigate the potential contribution of oxidative damage and antioxidant status to neurodegeneration in EGS. Methods: Systemic levels of surrogate biomarkers were determined in 10 horses with acute EGS and in 2 control populations; 10 healthy horses co-grazing with the 10 EGS horses at the onset of clinical disease, and 10 healthy mares grazing where EGS has not been reported. Results: EGS horses had alterations in levels of several antioxidants, consistent with oxidative stress, the acute phase response and/or the secondary metabolic complications of EGS. EGS horses had elevated plasma dihydroxyphenylalanine (DOPA) levels. Conclusions: The elevated DOPA levels probably reflected a generalised disturbance of catecholamine metabolism rather than increased DOPA production via free radical-mediated oxidation of tyrosine. However, there was no evidence of systemic macromolecular oxidative damage. Potential clinical relevance: Further work is required to determine whether macromolecular oxidative damage occurring at the neuronal level contributes to EGS. [source] Cyclical ischaemic preconditioning modulates the adaptive immune response in human limb ischaemia,reperfusion injuryBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2009P. J. Sullivan Background: Reperfusion injury (RI) has significant local and systemic consequences. Ischaemic preconditioning (IPC) modulates RI and the innate immune response. This study examined whether IPC attenuates RI-mediated changes in lymphocyte populations and function following elective surgery. Methods: Twenty-five patients sustaining 1 h of tourniquet ischaemia during cruciate ligament reconstruction were randomized before surgery to three 5-min ischaemia cycles separated by 5 min of reperfusion, or to a control group. Systemic levels of interleukin (IL) 4 and interferon (IFN) ,, and surface expression of CD45ro/ra, CD62L and CD95 were measured. T cells were examined systemically and in stimulated serum co-culture to determine CD4/CD8 and Th1/Th2 shifts through intracellular cytokine production. Results: CD4 CD45ro cell numbers increased after RI without IPC, whereas CD8 cells expressing CD45ro and CD95 increased with IPC. Preconditioned serum in co-culture attenuated increases in CD4 and decreases in CD8 numbers, a process prevented by inhibition of antigen activation. Following RI, systemic IL-2 levels were significantly lower after IPC, whereas co-culture with post-RI serum increased proinflammatory intracellular cytokine production. Conclusion: IPC modulated T cell responses in limb RI through reduced activation and proinflammatory cytokine production by CD4 cells, while preventing CD4/CD8 derangement. IPC prevented lymphocyte-directed immune dysfunction. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Systemic levels of plasmin,antiplasmin complexes are correlated with the expansion rate of small abdominal aortic aneurysmsBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2001J. S. Lindholt Background: The cystatine proteolytic system, the serine proteolytic system and the metallodependent proteolytic system have all been reported to be involved in the matrix degradation of the aortic wall, causing abdominal aortic aneurysm (AAA). Plasmin is a common activator of all three systems and could theoretically be involved in the pathogenesis of AAA by activating all three systems. However, plasmin is immediately inactivated by antiplasmin, forming plasmin,antiplasmin (PAP) complexes when it reaches the circulation. This study was designed to assess whether the systemic levels of PAP complex in conservatively treated patients with AAA could be related to the natural history of AAA. Methods: In 1994, 112 of 141 men with AAA (greater than 3 cm) diagnosed by population screening were interviewed, examined, and had blood samples taken and prepared for serum and ethylenediamine tetra-acetic acid plasma by a standard method. The serum and plasma were frozen at , 21°C until analysis. Of the 112 patients, 99 were followed with annual control scans and blood pressure measurements for 1,5 (mean 2·5) years, and were referred for operation if the AAA exceeded 5 cm in diameter. Of the 99 patients, a random sample of 70 had their level of PAP complexes determined (Dade Behring, Rødovre, Denmark). Furthermore, the level of serum elastin peptides (SEPs) was determined by enzyme-linked immunosorbent assay. Spearman's rank sum correlation test, multivariate linear regression analysis and receiver,operator characteristic (ROC) curve analysis were used for statistical analysis (SPSS 10.0; SPSS, Chicago, Illinois, USA). Results: The level of PAP complex was positively correlated with annual expansion rate (r = 0·29, P = 0·01), but not with the initial AAA size (r = 0·17, P = 0·16) or SEP (r = 0·04, P = 0·77). The significant association to expansion persisted after adjustment for initial AAA size, SEP and smoking. Furthermore, the level of PAP complex was significantly predictive for AAAs expanding to operation recommendable size (area under ROC curve 65 per cent), with an optimal sensitivity and specificity of 65 and 67 per cent respectively. SEP level was also significantly predictive for AAAs expanding to operation recommendable size (area under ROC curve 56 per cent), with an optimal sensitivity and specificity of 56 and 57 per cent. Conclusion: The progression of AAA seems to be caused by a general activation of the proteolytic systems involving plasmin and not by genetic or environmental factors causing increased activation of specific proteases or decreased activity of their specific inhibitors. Furthermore, the level of PAP complex in patients with an aneurysm seems to have a better and independently predictive value of the natural history of AAA, compared with the best serological predictor known to date, the serum level of elastin peptides. © 2001 British Journal of Surgery Society Ltd [source] Role of mechanical factors in governing muscle blood flowACTA PHYSIOLOGICA, Issue 4 2010D. D. Sheriff Overview This study evaluates how mechanical factors impact cardiac output at the systemic level, and how mechanical factors influence muscle blood flow at the local level. Importantly, the two are intertwined; events that work locally in the periphery to augment muscle blood flow can also act centrally to contribute to the development of a high cardiac output. [source] STRATEGIES AND NEED FOR SYSTEMS CHANGEFAMILY COURT REVIEW, Issue 2 2000Improving Court Practice for the Millennium Chief Judge Judith S. Kaye of New York delivered the following address to the Millennium Conference of the National Council of Juvenile and Family Court Judges in Washington, D.C., on November 15, 1999. In it, she describes the development of the philosophy of the family court in the past century. Judge Kaye describes the family court's transition from reliance on social science to the incorporation of procedural due process guarantees in the Gault decision. She suggests that a further transformation is required to meet the needs of children and families in the 21st century. Judge Kaye proposes that in the next millennium the family court abandon the "remote adjudicator" judge who evolved after Gault to a "problem-solving model of judging, a judge who looks at the issues that are driving the caseload, who looks at the results that are being achieved, and who uses a hands-on style to figure out how we might do better both in individual cases and on a systemic level." The New York Times described Chief Justice Kaye as, "A dedicated and effective reformer of the state's sprawling court system. Each of her hard won changes has had a positive impact." Chief Judge Kaye recently received the National Center for State Courts' William H. Rhenquist Award for Judicial Excellence in November 1999. On the occasion of the award, Roger K. Warren, president of the National Center, observed about her,"There are many who are working hard to better process the many cases that come before the state courts, but there are few working an harder or more successfully to better serve the people who use the state courts." [source] Increased serum anandamide level at ruptured plaque site in patients with acute myocardial infarctionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2009Naotaka Maeda Abstract Inflammation caused by activated macrophages and T lymphocytes may trigger plaque rapture in acute coronary syndrome (ACS). Anandamide and 2-arachidonylglycerol (2-AG) are macrophage-derived signal lipids and may be involved in the pathogenesis of ACS, but no clinical relevant data have been reported. In 43 acute myocardial infarction (AMI) patients (66 ± 2 years), blood samples were obtained from the aortic root and the infarct-related coronary artery (IRA) using a PercuSurge system during primary percutaneous coronary intervention (PCI). In six patients with stable effort angina (SEA) (56 ± 6 years), blood samples were obtained from the site of stenosis during elective PCI. In 25 of the 43 AMI patients, anandamide was detected in the serum. Serum anandamide level was 35 ± 20 pmol/mL in the aorta and was significantly increased to 401 ± 134 pmol/mL in the IRA (P < 0.01). 2-AG was undetectable in most of the patients. In patients with SEA, neither anandamide nor 2-AG was detected in the serum at the plaque site. In AMI patients with anandamide detected, left ventricular ejection fraction at 2 weeks after PCI was increased by 3.7 ± 2.1% compared with that at the acute phase, while it was decreased by 3.0 ± 1.8% in those without anandamide detected (P < 0.05). The serum anandamide level at the culprit lesion was elevated compared with the systemic level in a significant number of AMI patients, indicating the synthesis of anandamide at the IRA. Anandamide was suggested to be derived from ruptured plaque and may exert beneficial effects in humans. [source] Cumulative effects of in utero administration of mixtures of reproductive toxicants that disrupt common target tissues via diverse mechanisms of toxicityINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010C. V. Rider Summary Although risk assessments are typically conducted on a chemical-by-chemical basis, the 1996 Food Quality Protection Act required the US Environmental Protection Agency to consider cumulative risk of chemicals that act via a common mechanism of toxicity. To this end, we are conducting studies with mixtures of chemicals to elucidate mechanisms of joint action at the systemic level with the goal of providing a framework for assessing the cumulative effects of reproductive toxicants. Previous mixture studies conducted with antiandrogenic chemicals are reviewed briefly and two new studies are described. In all binary mixture studies, rats were dosed during pregnancy with chemicals, singly or in pairs, at dosage levels equivalent to approximately one-half of the ED50 for hypospadias or epididymal agenesis. The binary mixtures included androgen receptor (AR) antagonists (vinclozolin plus procymidone), phthalate esters [di(n-butyl) phthalate (DBP) plus benzyl n-butyl phthalate (BBP) and diethyl hexyl phthalate (DEHP) plus DBP], a phthalate ester plus an AR antagonist (DBP plus procymidone), a mixed mechanism androgen signalling disruptor (linuron) plus BBP, and two chemicals which disrupt epididymal differentiation through entirely different toxicity pathways: DBP (AR pathway) plus 2,3,7,8 TCDD (AhR pathway). We also conducted multi-component mixture studies combining several ,antiandrogens'. In the first study, seven chemicals (four pesticides and three phthalates) that elicit antiandrogenic effects at two different sites in the androgen signalling pathway (i.e. AR antagonist or inhibition of androgen synthesis) were combined. In the second study, three additional phthalates were added to make a 10 chemical mixture. In both the binary mixture studies and the multi-component mixture studies, chemicals that targeted male reproductive tract development displayed cumulative effects that exceeded predictions based on a response-addition model and most often were in accordance with predictions based on dose-addition models. In summary, our results indicate that compounds that act by disparate mechanisms of toxicity to disrupt the dynamic interactions among the interconnected signalling pathways in differentiating tissues produce cumulative dose-additive effects, regardless of the mechanism or mode of action of the individual mixture component. [source] Intranasal immunization using biphasic lipid vesicles as delivery systems for OmlA bacterial protein antigen and CpG oligonucleotides adjuvant in a mouse modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2005V. L. Alcón The nasal mucosa is an important arm of the mucosal system since it is often the first point of contact for inhaled antigens. The ineffectiveness of the simple delivery of soluble antigens to mucosal membranes for immunization has stimulated extensive studies in appropriate delivery systems and adjuvants. We have evaluated biphasic lipid vesicles as a novel intranasal (i.n.) delivery system (designated as vaccine targeting adjuvant, VTA) containing bacterial antigens and CpG oligode-oxynucleotides (ODNs). Results show that administration of antigen and CpG ODNs in biphasic lipid vesicles resulted in greater induction of IgA levels in serum (P<0.05) and mucosal antibody responses such as IgA in nasal secretions and lung (P<0.01) after immunization with a combined subcutaneous (s.c.)/i.n. as compared to s.c./s.c. approach. Based on antibody responses, VTA formulations were found to be suitable as delivery systems for antigens and CpG ODNs by the intranasal route, resulting in a Th2-type of immune response, characterized by IgG1 and IL-4 production at the systemic level. [source] Polychromatic Light Similar to the Terrestrial Solar Spectrum Without its UV Component Stimulates DNA Synthesis in Human Peripheral Blood Lymphocytes In Vivo and In VitroPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2006Natalya A. Zhevago ABSTRACT Immunosuppressive effects of the minor component of the terrestrial solar spectrum, UV radiation, have been substantiated over the past several years. This raises the question of what influence the dominant part of the solar spectrum,visible and IR light,would have on the human immune system. In the present randomized, placebo-controlled double-blind study a small area of the body surface of volunteers was irradiated with polychromatic light (480,3400 nm), simulating the significant part of the terrestial sunlight irradiance spectrum and its power density. An average 2.5-fold to three-fold increase in spontaneous and phytohemagglutinin-induced DNA synthesis in peripheral blood lymphocytes (Lym) was revealed at 0.5,24 h after irradiation at a therapeutic dose (12 J/cm2) in subjects with low preirradiation levels of both processes. The in vivo findings were echoed in parallel in vitro experiments, when blood drawn from the same subjects was directly irradiated (2.4 J/cm2), or when the irradiated blood was mixed 1:10 with nonirradiated autolo-gous blood to model events in the circulation following transcutaneous blood photomodification. Our data suggest that exposure of the human body to polychromatic visible + IR light may photomodify blood in the dermal vasculature of the irradiated area to lead to an immediate transfer of the light-induced effects to Lym of the entire circulating blood, which can result in modulation of Lym functional state at the systemic level. [source] Adaptation of the Human Skin by Chronic Solar-simulating UV Irradiation Prevents Ultraviolet-B Irradiation-induced Rise in Serum C-Reactive Protein Levels,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2005Jarmo K. Laihia ABSTRACT Exposure of the skin to UV radiation induces local inflammation. We hypothesized that inflammation induced by erythemal UV-B irradiation could elevate levels of serum C-reactive protein (CRP) and that suberythemal repeating doses of solar-simulating UV radiation (SSR) would produce photoadaptation to such inflammation. Separation-free high-sensitivity assays of CRP show an increase by 42% (P= 0.046) in CRP concentrations in healthy human subjects 24 h after a 3 minimal erythemal dose (MED) dose of UV-B delivered onto a 100 cm2 skin area. Preceding daily suberythemal doses of whole-body SSR for 10 or 30 consecutive days completely prevented the CRP increase. UV-B-induced skin erythema was partially attenuated by 30 preceding days of SSR only (P= 0.00066). After 10 daily SSR doses, the mean baseline CRP concentrations (0.24 ± 0.21 mg/L) declined by 35% (P= 0.018). Using high-sensitivity analysis of serum CRP as the endpoint marker for cutaneous inflammation, we show that acute exposure of even a relatively small skin area to erythemal UV-B induces skin inflammation detectable also at the systemic level and that photoadaptation by preceding repeating suberythemal doses of SSR reduces signs of inflammation. Our data complement the view given by previous studies in that local photoadaptation also has systemic manifestations. [source] Contested hybridization of regulation: Failure of the Dutch regulatory system to protect minors from harmful mediaREGULATION & GOVERNANCE, Issue 2 2010Bärbel R. Dorbeck-Jung Abstract The hybridization of regulatory modes and instruments is currently a popular way to improve public regulation. However, it is still unclear whether combinations of hard law and soft law, co-regulation, and legally enforced self-regulation really make regulation more effective. Using the analytical framework of the "really responsive regulation" approach, in this article we explore effectiveness problems in a hybrid regulatory system that tries to protect minors from harmful media. In our analysis of low compliance rates in the context of system failures, we argue that effectiveness problems seem to arise from poorly informed staff members, lack of internal and external controls, low rule enforcement, insufficient overlap between public and private interests, poor social responsibility in the Dutch media sector, deficiencies in the institutional framework, an inconsistent regulatory strategy, and inadequate responses from responsible regulators. Furthermore, based on our case study we argue that institutional dynamics of standard-setting activities can be detrimental to regulatory goal achievement if there is no compensation at the systemic level. Ongoing "regulatory care" through control, corrective responses, and rule enforcement seems to be crucial for a hybrid regulatory system to perform well. [source] Increased activity of plasma and tissue kallikreins, plasma kininase II and salivary kallikrein in pemphigus foliaceus (fogo selvagem)BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2005T.B. Rosatelli Summary Background, Pemphigus foliaceus (PF) is an autoimmune blistering disease of unknown aetiology, which is endemic in Brazil. Although the pathogenesis of PF is still unknown, proteins of the contact system have been implicated. Objectives, As the components of the kinin system may interact with those of the contact system, in this study we evaluated the plasma levels of high-molecular-weight kininogen (HK) and low-molecular-weight kininogen (LK), and the activity of plasma kallikrein, tissue kallikrein and kininase II in plasma of patients with PF presenting with Nikolsky's sign. As kidneys and salivary glands are relevant sources of tissue kallikrein for plasma, we also evaluated urinary/salivary kallikrein and urinary kininase II activities. Methods, Fifteen patients and 15 age- and sex-matched controls were studied. Kininogen levels were determined by enzyme-linked immunosorbent assay, and the activities of kallikreins and kininase II were determined using selective chromogenic substrates. Results, Compared with controls, plasma HK levels were decreased (P = 0·031), whereas the activities of plasma kallikrein, tissue kallikrein and kininase II in plasma, and the activity of salivary kallikrein, were increased in patients (P < 0·001 for each comparison). Plasma levels of LK and the activities of urinary kallikrein and urinary kininase II were not significantly different from controls. Conclusions, Diminished levels of HK associated with increased activities of plasma kallikrein and kininase II indicate that the kinin system is activated at the systemic level in PF. As active plasma kallikreins may act on some proteins of the contact system, it is possible that the enzyme may contribute to blister formation. The further observation of an increased tissue kallikrein activity at the systemic and saliva levels may be interpreted as a systemic reflex of skin inflammation. Whether the activation of the kinin system is a cause or a consequence of blister formation needs further clarification. [source] Enhancing systems-thinking skills with modellingBRITISH JOURNAL OF EDUCATIONAL TECHNOLOGY, Issue 6 2008Woei Hung Systems thinking is an essential cognitive skill that enables individuals to develop an integrative understanding of a given subject at the conceptual and systemic level. Yet, systems thinking is not usually an innate skill. Helping students develop systems-thinking skills warrants attention from educators. This paper describes a study examining the effects of utilising systems modelling as a cognitive tool in enhancing a group of graduate students' systems-thinking skills. A significant improvement was observed in the systems-thinking practises of the students. A theoretical rationale for enhancing systems-thinking skills with modelling and the results of the study will be discussed. [source] Ex vivo TCR-induced leukocyte gene expression of inflammatory mediators is increased in type 1 diabetic patients but not in overweight childrenDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2010Jaime S. Rosa Abstract Background Abnormal systemic concentrations of proinflammatory cytokines/chemokines have been implicated in the development of long-term cardiovascular complications in type 1 diabetes (T1DM) and obesity. Whether leukocyte white blood cell (WBC) gene expression of these proinflammatory mediators contributes to their increased systemic levels, however, remains unclear, especially in the pediatric patient populations. This study examines mRNA changes of 9 cytokines and chemokines in WBCs following ex vivo immunostimulation from 9 T1DM (13.4 ± 0.5 year, 4F/5 M), 23 overweight (OW, 12.3 ± 0.5 year, 10F/13M, BMI% 97.1 ± 0.5 and > 90.0), and 21 healthy (CL, 13.8 ± 0.7 year, 9F/12 M, BMI% 59.6 ± 4.6 and < 85.0) children. Methods All subjects had been maintained in euglycemic conditions for at least 90 min before blood draws. Whole blood was then sampled and incubated with anti-T-cell receptor (TCR) antibody or heat-aggregated IgG (HAG) to stimulate T-cell and Fc receptors (FcR), respectively. After lysis of leukocytes, mRNA levels of six tumor necrosis factor superfamily cytokines (TNFSF2, 5, 6, 7, 9, 14) and three chemokines (CCL8, 20, and CXCL10) were measured using RT-PCR. Results Following TCR stimulation, T1DM displayed significantly greater mRNA responses than CL for TNFSF5, 7, 9, and CCL8, and CXCL10; TNFSF9, CCL8, and CXCL10 were also significantly higher in T1DM than OW; no difference was observed between OW and CL. FcR stimulation induced similar responses across groups. Conclusions Leukocytes of T1DM children displayed exaggerated gene expression in response to ex vivo TCR induction of five key proinflammatory cytokines/chemokines. This elevated leukocyte gene expression may be one of the pathophysiological contributors to the development of vascular complications in T1DM. Copyright © 2009 John Wiley & Sons, Ltd. [source] Myocardial lipofuscin-laden lysosomes contain the apoptosis marker caspase-cleaved cytokeratin-18EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2008A. Soleiman ABSTRACT Background Acute coronary syndrome is related to increased circulatory concentration of soluble apoptosis specific caspase-cleaved cytokeratin-18 (ccCK-18). Potential cardiac sources of this intermediate filament derivative have not been investigated to date. Materials and methods Paraffin embedded tissue of normal myocardium, and chronically damaged samples of ischaemic, congestive and hypertrophic cardiomyopathy were analysed by histology and by CK-8, CK-18, ccCK-18 immunohistochemistry (each group, n = 15). Antibody specificity of the ccCK-18 antibody M30 was checked by immunoblotting on lysed myocardium and enriched myocardial lysosomes. Results ccCK-18 and CK-18 but not CK-8 were present in all forms of cardiomyopathy, most prominently in ischaemic cardiomyopathy while only traces were detectable immunohistochemically in normal myocardium. Weak CK-18 and strong ccCK-18 staining co-localized to lysosomes with cardiac age pigment lipofuscin. Weak staining of CK-18 was detected in the cytoplasm of coronary endothelia. Conclusion Our study reveals that cardiac lipofuscin-laden lysosomes contain ccCK-18, a marker of apoptosis and its precursor CK-18. This ccCK-18 pool might contribute to increased systemic levels of ccCK-18 in acute coronary syndrome thus monitoring myocardial damage. [source] Systemic increase in type,I interferon activity in Sjögren's syndrome: A putative role for plasmacytoid dendritic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Manon Abstract In the salivary glands of primary Sjögren's syndrome (pSjS) patients, type,I IFN activity is increased, but systemic levels of type,I IFN proteins are rarely detected. This study focused on the systemic activity of type,I IFN in pSjS, as well as the role of peripheral plasmacytoid dendritic cells (pDC). Monocytes obtained from pSjS patients showed an increased expression of 40,genes. Twenty-three of these genes (58%), including IFI27, IFITM1, IFIT3 and IFI44, were inducible by type,I IFN. pSjS serum had an enhanced capability of inducing IFI27, IFITM1, IFIT3 and IFI44 in the monocytic cell line THP-1, likely due to the action of IFN-,. This effect could be inhibited by blocking the type,I IFN receptor, supporting a high type,I IFN bioactivity in pSjS serum. In addition, circulatory pDC showed increased expression of CD40. This expression was correlated to the expression level of the type,I IFN-regulated genes IFI27 and IFITM1 in monocytes of the same individual. This study indicates that the increased type,I IFN activity observed in pSjS patients is not only a local but also a systemic phenomenon and points to pDC as a possible source of this activity. [source] Activated NKT cells increase dendritic cell migration and enhance CD8+ T cell responses in the skinEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2006Anton Abstract Activated NKT cells produce cytokines such as IL-4 and IFN-, that function locally to influence the strength and functional development of antigen-specific T cells. Here we identify an alternative mechanism by which NKT cells influence the strength of T cell responses: through modulation of peripheral dendritic cell (DC) trafficking. NKT cell activation with ,-galactosylceramide induced high systemic levels of TNF-, that mediated increased DC migration from skin to draining lymph nodes. This increased DC trafficking led to a threefold increase in effector T cell priming and in the immune response elicited to antigen challenge when ,-galactosylceramide was given at the time of immunization of the skin. These studies provide important implications for the use of NKT cell activation strategies to manipulate T cell-mediated responses including responses to cutaneous tumors and graft vs. host disease. [source] Bifidobacterium longum lysate, a new ingredient for reactive skinEXPERIMENTAL DERMATOLOGY, Issue 8 2010Audrey Guéniche Please cite this paper as: Bifidobacterium longum lysate, a new ingredient for reactive skin. Experimental Dermatology 2010; 19: e1,e8. Abstract:, Reactive skin is characterized by marked sensitivity to physical (heat, cold, wind) or chemical (topically applied products) stimuli and by the impairment of the skin barrier's ability to repair itself. Several lines of evidence suggest that beyond their capacity to positively influence the composition of intestinal microbiota, some probiotic bacteria can modulate the immune system both at local and systemic levels, thereby improving immune defense mechanisms and/or down-regulating immune disorders such as allergies and intestinal inflammation. Several recent human clinical trials clearly suggest that probiotic supplementation might be beneficial to the skin. Using a probiotic lysate, Bifidobacterium longum sp. extract (BL), we demonstrated first in vitro, and then in a clinical trial, that this non-replicating bacteria form applied to the skin was able to improve sensitive skin. The effect of BL were evaluated first on two different models. Using ex vivo human skin explant model we found a statistically significant improvement versus placebo in various parameters associated with inflammation such as a decrease in vasodilation, oedema, mast cell degranulation and TNF-alpha release. Moreover, using nerve cell cultures in vitro, we showed that after 6 h of incubation in culture medium (0.3,1%), the probiotic lysate significantly inhibited capsaicin-induced CGRP release by neurones. Then, a topical cream containing the active extract was tested in a randomized, double-blind, placebo-controlled trial. Sixty-six female volunteers with reactive skin were randomly given either the cream with the bacterial extract at 10% (n = 33) or the control cream (n = 33). The volunteers applied the cream to the face, arms and legs twice a day for two months. Skin sensitivity was assessed by stinging test (lactic acid) and skin barrier recovery was evaluated by measuring trans-epidermal water loss following barrier disruption induced by repeated tape-stripping at D1, D29 and D57. The results demonstrated that the volunteers who applied the cream with bacterial extract had a significant decrease in skin sensitivity at the end of the treatment. Moreover, the treatment led to increase skin resistance against physical and chemical aggression compared to the group of volunteers who applied the control cream. Notably, the number of strippings required to disrupt skin barrier function was significantly increased for volunteers treated with the active cream. Clinical and self-assessment scores revealed a significant decrease in skin dryness after 29 days for volunteers treated with the cream containing the 10% bacterial extract. Since in vitro studies demonstrated that, on one hand, isolate sensitive neurones release less CGRP under capsaicin stimulation in the presence of the bacterial extract and, on the other hand, increased skin resistance in volunteers applying the test cream, we speculate that this new ingredient may decrease skin sensitivity by reducing neurone reactivity and neurone accessibility. The results of this studies demonstrate that this specific bacterial extract has a beneficial effect on reactive skin. These findings suggest that new approaches, based on a bacteria lysate, could be developed for the treatment and/or prevention of symptoms related to reactive skin. [source] Controlled Growth Factor Delivery for Tissue EngineeringADVANCED MATERIALS, Issue 32-33 2009Prakriti Tayalia Abstract Growth factors play a crucial role in information transfer between cells and their microenvironment in tissue engineering and regeneration. They initiate their action by binding to specific receptors on the surface of target cells and the chemical identity, concentration, duration, and context of these growth factors contain information that dictates cell fate. Hence, the importance of exogenous delivery of these molecules in tissue engineering is unsurprising, considering their importance for tissue regeneration. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and their potential toxicity at high systemic levels, suggest that conventional routes of administration are unlikely to be effective. In this review, we provide an overview of the design criteria for growth factor delivery vehicles with respect to the growth factor itself and the microenvironment for delivery. We discuss various methodologies that could be adopted to achieve this localized delivery, and strategies using polymers as delivery vehicles in particular. [source] Comparison of the Systemic Levels of Inflammatory Markers after Percutaneous Coronary Intervention with Bare Metal versus Sirolimus-Eluting StentsJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2009ABDALLAH G. REBEIZ M.D., F.A.C.C. Background: Percutaneous coronary intervention (PCI) with bare metal stent (BMS) deployment causes plaque disruption and a rise in systemic levels of C-reactive protein (CRP), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. Our aim is to study whether PCI with sirolimus-eluting stent (SES) use attenuates this response. Methods: Patients with stable angina undergoing single-vessel PCI were enrolled in a randomized, open-label fashion into a BMS group or an SES group. Blood samples were drawn pre-PCI, 24 hours post-PCI, and 30 days post-PCI. Systemic concentrations of CRP, IL-6, and MCP-1 were measured at all time points. Results: In total, 41 patients were enrolled (21 in the BMS group and 20 in the SES group). The baseline plasma concentrations of all markers were comparable between groups. At 24 hours, the mean plasma CRP concentration in the SES group was 20.21 mg/dL versus 8.95 mg/dL in the BMS group (P = 0.15). The mean plasma IL-6 concentration at 24 hours was 25.41 pg/mL in the SES group versus 17.44 pg/mL in the BMS group (P = 0.17). The mean plasma MCP-1 concentration at 24 hours was 382.38 pg/mL in the SES group versus 329.04 pg/mL in the BMS group (P = 0.2). At 30 days, plasma concentrations of all three markers decreased to similar values between groups. Conclusions: The use of SES did not inhibit the rise in systemic concentrations of CRP, IL-6, and MCP-1 at 24 hours or 30 days post-PCI, compared with BMS. Moreover, at 24 hours, there was a trend for higher systemic levels of all proinflammatory markers in the SES group compared with the BMS cohort. [source] Phytomodulatory potentials of Aloe vera against Salmonella OmpR -mediated inflammationPHYTOTHERAPY RESEARCH, Issue 8 2008Praveen Rishi Abstract Mediators released during inflammatory response play an essential role in eliminating microbes or microbial products. However, the uncontrolled release of cytotoxic substances characterized by extensive inflammation may adversely affect normal tissues. Under such conditions it is important to manage the hyperinflammation in order to change the clinical manifestations of the disease. Accordingly, the present study was designed to evaluate the modulation of Salmonella OmpR mediated inflammation by Aloe vera, a plant known to contain antiinflammatory ingredients. It was observed that outer-membrane proteins (OMPs) extracted from the wild type strain of S. typhimurium caused inflammation of greater magnitude compared with the OMPs extracted from its mutant construct as evident from the oedema test as well as the hyperalgesic (flicking) response of the animals under experimental conditions. However, Aloe vera applied topically, administered intraperitoneally or in combination modulated the inflammatory response. The maximum effect was observed with the combined formulation indicating modulation at local as well as systemic levels. The results reveal that this modulation could be due to the potential of Aloe vera to decrease peroxidative damage via a decrease in the levels of monokines (TNF- ,, IL-1 and IL-6) and an increase in the level of superoxide dismutase (SOD). Moreover, the presence of SOD in Aloe vera itself might be responsible for enhancing its levels in the macrophages. On the other hand, no significant change in the catalase activity was observed by Aloe vera treatment. The use of Aloe vera, therefore, seems to have a promising role in the modulation of Salmonella OmpR mediated inflammation. Copyright © 2008 John Wiley & Sons, Ltd. [source] Developing strategies for detection of gene dopingTHE JOURNAL OF GENE MEDICINE, Issue 1 2008Anna Baoutina Abstract It is feared that the use of gene transfer technology to enhance athletic performance, the practice that has received the term ,gene doping', may soon become a real threat to the world of sport. As recognised by the anti-doping community, gene doping, like doping in any form, undermines principles of fair play in sport and most importantly, involves major health risks to athletes who partake in gene doping. One attraction of gene doping for such athletes and their entourage lies in the apparent difficulty of detecting its use. Since the realisation of the threat of gene doping to sport in 2001, the anti-doping community and scientists from different disciplines concerned with potential misuse of gene therapy technologies for performance enhancement have focused extensive efforts on developing robust methods for gene doping detection which could be used by the World Anti-Doping Agency to monitor athletes and would meet the requirements of a legally defensible test. Here we review the approaches and technologies which are being evaluated for the detection of gene doping, as well as for monitoring the efficacy of legitimate gene therapy, in relation to the detection target, the type of sample required for analysis and detection methods. We examine the accumulated knowledge on responses of the body, at both cellular and systemic levels, to gene transfer and evaluate strategies for gene doping detection based on current knowledge of gene technology, immunology, transcriptomics, proteomics, biochemistry and physiology. Copyright © 2008 John Wiley & Sons, Ltd. [source] Endogenous nitric oxide synthase inhibitors in sickle cell disease: abnormal levels and correlations with pulmonary hypertension, desaturation, haemolysis, organ dysfunction and deathBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2009Gregory J. Kato Summary Pulmonary hypertension (PH) in patients with sickle cell disease (SCD) is linked to intravascular haemolysis, impaired nitric oxide bioavailability, renal dysfunction, and early mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases (NOS), is associated with vascular disease in other populations. We determined the plasma concentrations for several key arginine metabolites and their relationships to clinical variables in 177 patients with SCD and 29 control subjects: ADMA, symmetric dimethylarginine (SDMA), NG-monomethyl L-arginine (L-NMMA), N-omega-hydroxy-L-arginine (NOHA), arginine and citrulline. The median ADMA was significantly higher in SCD than controls (0·94 ,mol/l vs. 0·31 ,mol/l, P < 0·001). Patients with homozygous SCD had a remarkably lower ratio of arginine to ADMA (50 ,mol/l vs. 237, P < 0·001). ADMA correlated with markers of haemolysis, low oxygen saturation and soluble adhesion molecules. PH was associated with high levels of ADMA and related metabolites. Higher ADMA level was associated with early mortality, remaining significant in a multivariate analysis. Subjects with homozygous SCD have high systemic levels of ADMA, associated with PH and early death, implicating ADMA as a functional NOS inhibitor in these patients. These defects and others converge on the nitric oxide pathway in homozygous SCD with vasculopathy. [source] Manipulation of the small intestine as a cause of the increased inflammatory response after open compared with laparoscopic surgery,,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2006N. Hiki Background: Laparoscopic surgery of the gastrointestinal tract involves a reduced immune response compared with open surgery. The aim of this study was to assess manual handling of the gut in open procedures as the principal cause of the enhanced immune response. Methods: Eighteen Landrace pigs underwent gastrectomy by three different methods: conventional open wound with bowel manipulation, laparoscopically assisted gastrectomy, and gastrectomy without manipulation using a combination of open wound and laparoscopic surgical devices. Local inflammatory changes were assessed by ascites formation, intestinal adhesion development and intestinal inflammatory gene expression. Associated systemic inflammatory changes were determined by measuring portal and systemic plasma endotoxin levels, plasma inflammatory cytokine levels, liver inflammatory gene expression and transaminase levels. Results: Significantly more postoperative intra-abdominal fluid and adhesions were seen in the open group. The expression of inflammatory cytokines was significantly greater in the intestine and liver in the open group. Portal and systemic levels of endotoxin, inflammatory cytokines and transaminases were also higher. Conclusion: Manual handling of organs during gastrectomy is an important contributor to the molecular and humoral inflammatory response to surgery, supporting the use of minimally invasive techniques in gastrointestinal surgery. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Systemic levels of plasmin,antiplasmin complexes are correlated with the expansion rate of small abdominal aortic aneurysmsBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2001J. S. Lindholt Background: The cystatine proteolytic system, the serine proteolytic system and the metallodependent proteolytic system have all been reported to be involved in the matrix degradation of the aortic wall, causing abdominal aortic aneurysm (AAA). Plasmin is a common activator of all three systems and could theoretically be involved in the pathogenesis of AAA by activating all three systems. However, plasmin is immediately inactivated by antiplasmin, forming plasmin,antiplasmin (PAP) complexes when it reaches the circulation. This study was designed to assess whether the systemic levels of PAP complex in conservatively treated patients with AAA could be related to the natural history of AAA. Methods: In 1994, 112 of 141 men with AAA (greater than 3 cm) diagnosed by population screening were interviewed, examined, and had blood samples taken and prepared for serum and ethylenediamine tetra-acetic acid plasma by a standard method. The serum and plasma were frozen at , 21°C until analysis. Of the 112 patients, 99 were followed with annual control scans and blood pressure measurements for 1,5 (mean 2·5) years, and were referred for operation if the AAA exceeded 5 cm in diameter. Of the 99 patients, a random sample of 70 had their level of PAP complexes determined (Dade Behring, Rødovre, Denmark). Furthermore, the level of serum elastin peptides (SEPs) was determined by enzyme-linked immunosorbent assay. Spearman's rank sum correlation test, multivariate linear regression analysis and receiver,operator characteristic (ROC) curve analysis were used for statistical analysis (SPSS 10.0; SPSS, Chicago, Illinois, USA). Results: The level of PAP complex was positively correlated with annual expansion rate (r = 0·29, P = 0·01), but not with the initial AAA size (r = 0·17, P = 0·16) or SEP (r = 0·04, P = 0·77). The significant association to expansion persisted after adjustment for initial AAA size, SEP and smoking. Furthermore, the level of PAP complex was significantly predictive for AAAs expanding to operation recommendable size (area under ROC curve 65 per cent), with an optimal sensitivity and specificity of 65 and 67 per cent respectively. SEP level was also significantly predictive for AAAs expanding to operation recommendable size (area under ROC curve 56 per cent), with an optimal sensitivity and specificity of 56 and 57 per cent. Conclusion: The progression of AAA seems to be caused by a general activation of the proteolytic systems involving plasmin and not by genetic or environmental factors causing increased activation of specific proteases or decreased activity of their specific inhibitors. Furthermore, the level of PAP complex in patients with an aneurysm seems to have a better and independently predictive value of the natural history of AAA, compared with the best serological predictor known to date, the serum level of elastin peptides. © 2001 British Journal of Surgery Society Ltd [source] | |||||||||||||||||||||||||