Mediators of Inflammation

Mediators of Inflammationhttp://www.hindawi.comThe latest articles from Hindawi Publishing Corporation© 2008, Hindawi Publishing Corporation. All rights reserved.The NALP3/Cryopyrin-Inflammasome Complex is Expressed in LPS-Induced Ocular Inflammationhttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/614345In the inflammosome complex, NALP3 or NALP1 binds to ASC and activates caspase-1 which induces IL-1β. In murine LPS-induced ocular inflammation, the production of IL-1β is increased. We suggest that NALP3- or NALP1-inflammasome complex can be participating in the LPS-induced ocular inflammation. In this work, eye, brain, testis, heart, spleen, and lung were obtained from C3H/HeN mice treated with LPS for 3 to 48 hours, and the expression of NALP1b, NALP3, ASC, caspase-1, IL-1β, and IL-18 was determined. Infiltrated leukocytes producing IL-1β in the anterior chamber were found at 12-hour posttreatment. A high upregulated expression of NALP3, ASC, caspase-1, IL-1β, and IL-18 was found at the same time when infiltrated leukocytes were observed. NALP1b was not detected in the eye of treated mice. NALP3 was also overexpressed in heart and lung. These results suggest that NALP3-, but not NALP1-inflammosome complex, is participating in the murine LPS-induced ocular inflammation.José F. González-Benítez, Marco A. Juárez-Verdayes, Sandra Rodríguez-Martínez, Mario E. Cancino-Diaz, Francisco García-Vázquez, and Juan C. Cancino-Diaz© 2008, Hindawi Publishing Corporation. All rights reserved.Lymphotoxin-α Plays Only a Minor Role in Host Resistance to Respiratory Infection with Virulent Type A Francisella tularensis in Micehttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/239740This study examined the role of lymphotoxin (LT)-α in host defense against airborne infection with Francisella tularensis, a gram-negative facultative intracellular bacterium and the causative agent of tularemia. Following a low-dose aerosol infection with the highly virulent type A strain of F. tularensis, mice deficient in LT α (LTα−/−) consistently harbored approximately 10-fold fewer bacteria in their spleens at day 2 and 10-fold more bacteria in their lungs at day 4 than LTα+/+ mice. However, the mortality and median time to death were indistinguishable between the two mouse strains. In addition, the inflammatory responses to the infection, as reflected by the cytokine levels and leukocyte influx in the bronchoalveolar lavage fluid and histopathological analysis, were generally similar between LTα−/− and LTα+/+ mice. These data suggest that although LTα does not contribute significantly to the resistance and host responses of mice to airborne type A F. tularensis infection, it does play a subtle role in the multiplication/dissemination of F. tularensis.Deng Zhang, Rhonda KuoLee, Greg Harris, Qinxian Zhang, J. Wayne Conlan, and Wangxue Chen© 2008, Hindawi Publishing Corporation. All rights reserved.Inhibition of Angiogenic Factor Production from Murine Mast Cells by an Antiallergic Agent (Epinastine Hydrochloride) In Vitrohttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/265095Angiogenesis is an important event both in the development of allergic inflammatory responses and in the pathophysiology of tissue remodeling in allergic diseases. In the present study, therefore, we examined the influence of antihistamines on angiogenesis through the choice of epinastine hydrochloride (EP) and murine mast cells in vitro. Mast cells (5×105 cells/mL) presensitized with murine IgE specific for ovalbumin (OVA) were stimulated with 10 ng/mL OVA in the presence of various concentrations of EP for 4 hours. The levels of angiogenesis factors, keratinocyte-derived chemokine (KC), tumor necrosis factor-α (TNF), and vascular endothelial growth factor (VEGF) in culture supernatants, were examined by ELISA. We also examined mRNA expression for the angiogenesis factors by RT-PCR. EP significantly inhibited the production of KC, TNF, and VEGF induced by IgE-dependent mechanism at more than 25 ng/mL. Semiquantitative analysis using RT-PCR showed that EP also significantly reduced mRNA expressions for KC, TNF, and VEGF. These results strongly suggest that EP suppresses angiogenesis factor production through the inhibition of mRNA expression in mast cells and results in favorable modification of clinical conditions of allergic diseases.K. Asano, A. Furuta, K. Kanai, S. Sakaue, H. Suzaki, and T. Hisamitsu© 2008, Hindawi Publishing Corporation. All rights reserved.Expression of Endothelial Nitric Oxide Synthase and Endothelin-1 in Skin Tissue from Amputated Limbs of Patients with Complex Regional Pain Syndromehttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/680981Background and Objectives. Impaired microcirculation during the chronic stage of complex regional pain syndrome (CRPS) is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Endothelial dysfunction is suggested to be the main cause of diminished blood flow. The aim of this study was to examine the distribution of endothelial nitric oxide synthase (eNOS) and endothelin-1(ET-1) relative to vascular density represented by the endothelial marker CD31-immunoreactivity in the skin tissue of patients with chronic CRPS. Methods. We performed immunohistochemical staining on sections of skin specimens obtained from the amputated limbs (one arm and one leg) of two patients with CRPS. Results. In comparison to proximal specimens we found an increased number of migrated endothelial cells as well as an increase of eNOS activity in distal dermis specimens. Conclusions. We found indications that endothelial dysfunction plays a role in chronic CRPS.J. George Groeneweg, Claudia Heijmans Antonissen, Frank J. P. M. Huygen, and Freek J. Zijlstra© 2008, Hindawi Publishing Corporation. All rights reserved.Pro- and Anti-Inflammatory Cytokines Release in Mice Injected with Crotalus durissus terrificus Venomhttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/874962The effects of Crotalus durissus terrificus venom (Cdt) were analyzed with respect to the susceptibility and the inflammatory mediators in an experimental model of severe envenomation. BALB/c female mice injected intraperitoneally presented sensibility to Cdt, with changes in specific signs, blood biochemical and inflammatory mediators. The venom induced reduction of glucose and urea levels and an increment of creatinine levels in serum from mice. Significant differences were observed in the time-course of mediator levels in sera from mice injected with Cdt. The maximum levels of IL-6, NO, IL-5, TNF, IL-4 and IL-10 were observed 15 min, 30 min, 1, 2 and 4 hours post-injection, respectively. No difference was observed for levels of IFN-γ. Taken together, these data indicate that the envenomation by Cdt is regulated both pro- and anti-inflammatory cytokine responses at time-dependent manner. In serum from mice injected with Cdt at the two first hours revealed of pro-inflammatory dominance. However, with an increment of time an increase of anti-inflammatory cytokines was observed and the balance toward to anti-inflammatory dominance. In conclusion, the observation that Cdt affects the production of pro- and anti-inflammatory cytokines provides further evidence for the role played by Cdt in modulating pro/anti-inflammatory cytokine balance.A. Hernández Cruz, S. Garcia-Jimenez, R. Zucatelli Mendonça, and V. L. Petricevich© 2008, Hindawi Publishing Corporation. All rights reserved.Neutrophil and Monocyte CD64 and CD163 Expression in Critically Ill Neonates and Children with Sepsis: Comparison of Fluorescence Intensities and Calculated Indexeshttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/202646Objective. To evaluate the expression of CD64 and CD163 on neutrophils and monocytes in SIRS with/without sepsis and to compare the diagnostic accuracy of CD64 and CD163 molecules expression determined as (1) mean fluorescence intensities (MFI) of CD64 and CD163; and (2) the ratio (index) of linearized MFI to the fluorescence signal of standardized beads. Patients and methods. Fifty-six critically ill neonates and children with systemic inflammatory response syndrome (SIRS) and suspected sepsis, classified into two groups: SIRS with sepsis (n=29) and SIRS without sepsis (n=27). Results. CD64 and CD163 MFI measured on neutrophils and monocytes were elevated in patients with SIRS with sepsis. Diagnostic accuracy of indexes was equal to diagnostic accuracy of MFI for CD64 on neutrophils (0.833 versus 0.854 for day 0 and 0.975 versus 0.983 for day 1) and monocytes (0.811 versus 0.865 for day 0 and 0.825 versus 0.858 for day 1), and CD163 on neutrophils (0.595 versus 0.655 for day 0 and 0.677 versus 0.750 for day 1), but not for CD163 on monocytes. Conclusion. CD64 MFI, CD163 MFI, CD64 indexes for neutrophils and monocytes, and CD163 index for neutrophils can all be used for discrimination of SIRS and sepsis in critically ill neonates and children. CD64 index for neutrophils, however, is superior to all other markers.Mojca Groselj-Grenc, Alojz Ihan, and Metka Derganc© 2008, Hindawi Publishing Corporation. All rights reserved.Insulin Resistance: A Proinflammatory State Mediated by Lipid-Induced Signaling Dysfunction and Involved in Atherosclerotic Plaque Instabilityhttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/767623The dysregulation of the insulin-glucose axis represents the crucial event in insulin resistance syndrome. Insulin resistance increases atherogenesis and atherosclerotic plaque instability by inducing proinflammatory activities on vascular and immune cells. This condition characterizes several diseases, such as type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), obesity, hypertension, dyslipidemia, and other endocrinopathies, but also cancer. Recent studies suggest that the pathophysiology of insulin resistance is closely related to interferences with insulin-mediated intracellular signaling on skeletal muscle cells, hepatocytes, and adipocytes. Strong evidence supports the role of free fatty acids (FFAs) in promoting insulin resistance. The FFA-induced activation of protein kinase C (PKC) delta, inhibitor kappaB kinase (IKK), or c-Jun N-terminal kinase (JNK) modulates insulin-triggered intracellular pathway (classically known as PI3-K-dependent). Therefore, reduction of FFA levels represents a selective target for modulating insulin resistance.Fabrizio Montecucco, Sabine Steffens, and François Mach© 2008, Hindawi Publishing Corporation. All rights reserved.Six Years Follow-up of the Levels of TNF-α and IL-6 in Patients with Complex Regional Pain Syndrome Type 1http://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/469439In an earlier study, levels of the proinflammatory cytokines TNF-α and IL-6 are higher in blisters fluid from the complex regional pain syndrome type 1 (CRPS1) side obtained at 6 and 30 months (median) after the initial event. The aim of this follow-up study is to determine the involvement of these cytokines in long lasting CRPS1. Twelve CRPS1 patients, with median disease duration of 72 months, participated. The levels of TNF-α and IL-6 were measured in blister fluid; disease activity was reevaluated by measuring pain and differences in temperature, volume, and mobility between both extremities. Differences in levels of IL-6 and TNF-α and mobility between both sides were significantly decreased. Pain and differences in temperature and volume were not significantly altered. No correlation was found between the cytokines and the disease characteristics. These results indicate that IL-6 and TNF-α are only partially responsible for the signs and symptoms of CRPS1.Feikje Wesseldijk, Frank J. P. M. Huygen, Claudia Heijmans-Antonissen, Sjoerd P. Niehof, and Freek J. Zijlstra© 2008, Hindawi Publishing Corporation. All rights reserved.Serum Concentration of Interleukin-6 Is Increased Both in Active and Remission Stages of Pemphigus Vulgarishttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/875394As most studies on pemphigus vulgaris (PV) pathogenesis concern its active stage, we aimed to evaluate the serum concentration of TNF-α, IL-1, and IL-6 in PV patients in clinical remission. The study group consisted of sera from 19 PV patients in active stage and from 24 patients in clinical remission. 19 sera taken from healthy subjects served as the controls. Serum IL-6 concentrations in PV active and PV remission group were significantly higher when compared to the controls (P<.05). In patients in active stage of PV, a significant correlation between serum IL-1 and IL-6 concentrations was found (rP=0.46;P<.05). We also found a negative correlation between TNF-α level and pemphigus antibodies titer in the patients from the remission group (rS=−0.47303;P<.02). Our data suggest that IL-6 and TNF-α may be involved in maintaining immunological disturbances in remission stage of PV.Joanna Narbutt, Jolanta Lukamowicz, Jarosław Bogaczewicz, Anna Sysa-Jedrzejowska, Jolanta Dorota Torzecka, and Aleksandra Lesiak© 2008, Hindawi Publishing Corporation. All rights reserved.Increased Responsiveness to Toll-Like Receptor 4 Stimulation in Peripheral Blood Mononuclear Cells from Patients with Recent Onset Rheumatoid Arthritishttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/132732Background. Cell signaling via Toll-like receptors (TLRs) leads to synovial inflammation in rheumatoid arthritis (RA). We aimed to assess effects of TLR2 and TLR4 stimulation on proinflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with recent-onset RA, osteoarthrosis (OA), and healthy control (HC). Methods. PBMCs were stimulated with LPS, biglycan and cytokine mix. Cytokines were analyzed in supernatants with ELISA. Expression of toll-like receptors mRNA in leukocytes was analyzed using real-time qPCR. Results. PBMCs from RA patients spontaneously produced less IL-6 and TNFα than cells from OA and HC subjects. LPS increased cytokines' production in all groups. In RA patients increase was dramatic (30 to 48-fold and 17 to 31-fold, for respective cytokines) compared to moderate (2 to 8-fold) in other groups. LPS induced 15-HETE generation in PBMCs from RA (mean 251%) and OA patients (mean 43%), although only in OA group, the increase was significant. TLR2 and TLR4 gene expressions decreased in response to cytokine mix, while LPS enhanced TLR2 expression in HC and depressed TLR4 expression in OA patients. Conclusion. PBMCs from recent-onset RA patients are overresponsive to stimulation with bacterial lipopolysaccharide. TLR expression is differentially regulated in healthy and arthritic subjects.M. L. Kowalski, A. Wolska, J. Grzegorczyk, J. Hilt, M. Jarzebska, M. Drobniewski, M. Synder, and M. Kurowski© 2008, Hindawi Publishing Corporation. All rights reserved.Lipoperoxidation and Protein Oxidative Damage Exhibit Different Kinetics During Septic Shockhttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/168652Septic shock (SS)-related multiorgan dysfunction has been associated with oxidative damage, but little is known about the temporal damage profile and its relationship to severity. The present work investigated prospectively 21 SS patients. Blood samples were obtained at diagnosis, 24, 72 hours, day 7, and at 3 months. At admission, thiobarbituric acid reactive substances (TBARSs), plasma protein carbonyls, plasma protein methionine sulfoxide (MS), ferric/reducing antioxidant power (FRAP), total red blood cell glutathione (RBCG), uric acid (UA), and bilirrubin levels were increased (P<.05). Total radical—trapping antioxidant potential (TRAP) and vitamin-E were similar to controls, and vitamin-C was decreased (P<.05). During evolution, TBARS and RBCG increased (P<.001), vitamin-E levels remained stable, whereas plasma protein carbonyls and MS, TRAP, vitamin-C, reduced glutathione, and UA levels decreased (P<.006). After 3 months, plasma protein carbonyls and MS persisted elevated. More severe patients exhibited higher TBARS, TRAP, FRAP, vitamin-C, UA, and bilirrubin levels. Our results suggest early and persistent oxidative stress during septic shock and a correlation between increasing levels of lipoperoxidation and sepsis severity.Max Andresen, Tomas Regueira, Alejandro Bruhn, Druso Perez, Pablo Strobel, Alberto Dougnac, Guillermo Marshall, and Federico Leighton© 2008, Hindawi Publishing Corporation. All rights reserved.Prolonged Classical NF-κB Activation Prevents Autophagy upon E. coli Stimulation In Vitro: A Potential Resolving Mechanism of Inflammationhttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/725854Activation of NF-κB is known to prevent apoptosis but may also act as proapoptotic factor in order to eliminate inflammatory cells. Here, we show that classical NF-κB activation in RAW 264.7 and bone marrow-derived macrophages upon short E. coli coculture is necessary to promote cell death at late time points. At 48 hours subsequent to short-term, E. coli challenge increased survival of NF-κB-suppressed macrophages was associated with pattern of autophagy whereas macrophages with normal NF-κB signalling die. Cell death of normal macrophages was indicated by preceding downregulation of autophagy associated genes atg5 and beclin1. Restimulation of macrophages with LPS at 48 hours after E. coli treatment results in augmented proinflammatory cytokine production in NF-κB-suppressed macrophages compared to control cells. We thus demonstrate that classical NF-κB activation inhibits autophagy and promotes delayed programmed cell death. This mechanism is likely to prevent the recovery of inflammatory cells and thus contributes to the resolution of inflammation.Silke Schlottmann, Franziska Buback, Bettina Stahl, Rainer Meierhenrich, Paul Walther, Michael Georgieff, and Uwe Senftleben© 2008, Hindawi Publishing Corporation. All rights reserved.MCP-1 −2518 A/G Single Nucleotide Polymorphism in Slovak Patients with Systemic Sclerosishttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/204063Recent study in a group of German patients with SSc has implicated the SNP in the MCP-1 gene (−2518 A to G) as a factor of susceptibility to SSc. Reflecting the need for replication of genetic association studies, we investigated if this SNP is associated with SSc in another Caucasian population. MCP-1 −2518 A/G genotypes were determined using PCR-SSP in 46 SSc patients and in 449 healthy subjects, all unrelated and of Slovak (Slavonic) origin. The distribution of MCP-1 −2518 A/G genotypes complied with the Hardy-Weinberg equilibrium both in patient and healthy control groups. There was no difference in MCP-1 −2518∗G allele frequency between SSc patients and healthy subjects (patients: 0.23; controls: 0.24; P>.05). Furthermore, MCP-1 −2518 GG homozygotes were similarly represented among SSc patients and healthy subjects (P>.05). The association of MCP-1 −2518 A/G SNP with SSc observed originally in German population was not replicated in the Slovak population.Zdenka Navratilova, Jozef Lukac, Frantisek Mrazek, Eva Kriegova, Maria Bucova, Vladimir Bosak, and Martin Petrek© 2008, Hindawi Publishing Corporation. All rights reserved.Cord Blood Ischemia-Modified Albumin Levels in Normal and Intrauterine Growth Restricted Pregnancieshttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/523081Ischemia-modified albumin (IMA) is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR) may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals—‘‘brain sparing effect’’). Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA) full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035), and offspring of multigravidas (P = .021). In conclusion, ‘‘brain sparing effect’’ is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.Nicoletta Iacovidou, Despina D. Briana, Maria Boutsikou, Sophia Liosi, Stavroula Baka, <?layout cmd="newline"?> Theodora Boutsikou, Demetrios Hassiakos, and Ariadne Malamitsi-Puchner© 2008, Hindawi Publishing Corporation. All rights reserved.Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteinehttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/716458Although N-acetylcysteine (NAC) has been shown to be neuroprotective for traumatic brain injury (TBI), the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB) and inflammatory proteins such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1) after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.Gang Chen, Jixin Shi, Zhigang Hu, and Chunhua Hang© 2008, Hindawi Publishing Corporation. All rights reserved.Mycoplasma genitalium Lipoproteins Induce Human Monocytic Cell Expression of Proinflammatory Cytokines and Apoptosis by Activating Nuclear Factor κBhttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/195427This study was designed to investigate the molecular mechanisms responsible for the induction of proinflammatory cytokines gene expression and apoptosis in human monocytic cell line THP-1 stimulated by lipoproteins (LPs) prepared from Mycoplasma genitalium. Cultured cells were stimulated with M. genitalium LP to analyze the production of proinflammatory cytokines and expression of their mRNA by ELISA and RT-PCR, respectively. Cell apoptosis was also detected by Annexin V-FITC-propidium iodide (PI) staining and acridine orange (AO)-ethidium bromide (EB) staining. The DNA-binding activity of nuclear factor-κB (NF-κB) was assessed by electrophoretic mobility shift assay (EMSA). Results showed that LP stimulated THP-1 cells to produce tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in a dose-dependent manner. The mRNA levels were also upregulated in response to LP stimulation. LPs were also found to increase the DNA-binding activity of NF-κB, a possible mechanism for the induction of cytokine mRNA expression and the cell apoptosis. These effects were abrogated by PDTC, an inhibitor of NF-κB. Our results indicate that M. genitalium-derived LP may be an important etiological factor of certain diseases due to the ability of LP to produce proinflammatory cytokines and induction of apoptosis, which is probably mediated through the activation of NF-κB.Yimou Wu, Hong Qiu, Yanhua Zeng, Xiaoxing You, Zhongliang Deng, Minjun Yu, and Cuiming Zhu© 2008, Hindawi Publishing Corporation. All rights reserved.Inflammatory Breast Diseases during Lactation: Health Effects on the Newborn—A Literature Reviewhttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/298760Breastfeeding-associated inflammatory breast diseases appear especially during the first twelve weeks postpartum and are the most common reason for early cessation of breastfeeding. It also becomes increasingly evident that these inflammatory mammary diseases are triggered or perpetuated in a large part by psychosocial stress. Immunological processes taking place during this cascade in the mammary gland and consequences for the breastfeed newborn are mostly yet unknown. This review summarizes insights from studies on modulation of cytokine levels in breast milk during inflammatory processes like milk stasis and mastitis systematically. It also gives an overview on possible pathological effects, which these cytokine changes in the breast milk might have on the newborn.Achim Wöckel, Michael Abou-Dakn, Anna Beggel, and Petra Arck© 2008, Hindawi Publishing Corporation. All rights reserved.Effects of Nebivolol on Endothelial Gene Expression during Oxidative Stress in Human Umbilical Vein Endothelial Cellshttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/367590The endothelium plays a key role in the development of atherogenesis and its inflammatory and proliferative status influences the progression of atherosclerosis. The aim of this study is to compare the effects of two beta blockers such as nebivolol and atenolol on gene expression in human umbilical vein endothelial cells (HUVECs) following an oxidant stimulus. HUVECs were incubated with nebivolol or atenolol (10 micromol/L) for 24 hours and oxidative stress was induced by the addition of oxidized (ox)-LDL. Ox-LDL upregulated adhesion molecules (ICAM-1, ICAM-2, ICAM-3, E-selectin, and P-selectin); proteins linked to inflammation (IL-6 and TNFalpha), thrombotic state (tissue factor, PAI-1 and uPA), hypertension such as endothelin-1 (ET-1), and vascular remodeling such as metalloproteinases (MMP-2, MMP-9) and protease inhibitor (TIMP-1). The exposure of HUVECs to nebivolol, but not to atenolol, reduced these genes upregulated by oxidative stress both in terms of protein and RNA expression. The known antioxidant properties of the third generation beta blocker nebivolol seem to account to the observed differences seen when compared to atenolol and support the specific potential protective role of this beta blocker on the expression of a number of genes involved in the initiation and progression of atherosclerosis.Ulisse Garbin, Anna Fratta Pasini, Chiara Stranieri, Stefania Manfro, Chiara Mozzini, Veronica Boccioletti, Andrea Pasini, Mattia Cominacini, Stefano Evangelista, and Luciano Cominacini© 2008, Hindawi Publishing Corporation. All rights reserved.The Assessment of Autoimmunological Status and Prevalence of Different Forms of Celiac Disease among Children with Type 1 Diabetes Mellitus and Celiac Diseasehttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/285989This study aims to assess the autoimmunological status and forms of celiac disease (CD) among children with type 1 diabetes mellitus (T1DM) . The study group comprises 27 patients at the mean age of 12.30 years (±SD 3.12). The measurement of the level of diabetes-specific antibodies and organ-specific antibodies was gained at the T1DM-onset and repeated annually. The following risk factors influencing time of CD diagnosis were analyzed: age, sex, T1DM duration, autoantibodies, and HLA-haplotype. The prevalence of antibodies was GADA-74%, IAA-63%, IA2A-67%, ATA-11%, and ATG-4%. The intestinal biopsy revealed in 19% no changes and in 77% stage 3 (Marsh scale). In most cases, no clinical manifestation of CD was observed. The diagnosis of Hashimoto's disease was made twice. The negative correlation between the age at T1DM-onset and the interval between onset of T1DM and CD (r=‐0.35, p<.05) was noted. The high-comorbidity ratio of CD and thyroiditis with T1DM demands regular screening tests especially in the first years after T1DM-onset.Grazyna Deja, Anna Myrda, Przemyslawa Jarosz-Chobot, and Urszula Siekiera© 2008, Hindawi Publishing Corporation. All rights reserved.The NF-κB Inhibitor Curcumin Blocks Sepsis-Induced Muscle Proteolysishttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/317851We tested the hypothesis that treatment of rats with curcumin prevents sepsis-induced muscle protein degradation. In addition, we determined the influence of curcumin on different proteolytic pathways that are activated in septic muscle (i.e., ubiquitin-proteasome-, calpain-, and cathepsin L-dependent proteolysis) and examined the role of NF-κB and p38/MAP kinase inactivation in curcumin-induced inhibition of muscle protein breakdown. Rats were made septic by cecal ligation and puncture or were sham-operated. Groups of rats were treated with three intraperitoneal doses (600 mg/kg) of curcumin or corresponding volumes of solvent. Protein breakdown rates were measured as release of tyrosine from incubated extensor digitorum longus muscles. Treatment with curcumin prevented sepsis-induced increase in muscle protein breakdown. Surprisingly, the upregulated expression of the ubiquitin ligases atrogin-1 and MuRF1 was not influenced by curcumin. When muscles from septic rats were treated with curcumin in vitro, proteasome-, calpain-, and cathepsin L-dependent protein breakdown rates were reduced, and nuclear NF-κB/p65 expression and activity as well as levels of phosphorylated (activated) p38 were decreased. Results suggest that sepsis-induced muscle proteolysis can be blocked by curcumin and that this effect may, at least in part, be caused by inhibited NF-κB and p38 activities. The results also suggest that there is not an absolute correlation between changes in muscle protein breakdown rates and changes in atrogin-1 and MuRF1 expression during treatment of muscle wasting.Vitaliy Poylin, Moin U. Fareed, Patrick O'Neal, Nima Alamdari, Natasha Reilly, Michael Menconi, and Per-Olof Hasselgren© 2008, Hindawi Publishing Corporation. All rights reserved.Effects of Radix Adenophorae and Cyclosporine A on an OVA-Induced Murine Model of Asthma by Suppressing to T Cells Activity, Eosinophilia, and Bronchial Hyperresponsivenesshttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/781425The present study is performed to investigate the inhibitory effects of Radix Adenophorae extract (RAE) on ovalbumin-induced asthma murine model. To study the anti-inflammatory and antiasthmatic effects of RAE, we examined the development of pulmonary eosinophilic inflammation and inhibitory effects of T cells in murine by RAE and cyclosporine A (CsA). We examined determination of airway hyperresponsiveness, flow cytometric analysis (FACS), enzyme-linked immunosorbent assay (ELISA), quantitative real time (PCR), hematoxylin-eosin staining, and Masson trichrome staining in lung tissue, lung weight, total cells, and eosinophil numbers in lung tissue. We demonstrated how RAE suppressed development on inflammation and decreased airway damage.Seong-Soo Roh, Seung-Hyung Kim, Young-Cheol Lee, and Young-Bae Seo© 2008, Hindawi Publishing Corporation. All rights reserved.Platelet Counts and Platelet Activation Markers in Obese Subjectshttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/834153Objective. In this work we studied the correlation between platelet count, platelet activation, and systemic inflammation in overweight, obese, and morbidly obese individuals. Methods and subjects. A total of 6319 individuals participated in the study. Complete blood counts, high sensitivity C-reactive protein (hs-CRP) serum levels, and body mass index (BMI) were measured during routine checkups. Platelet activation markers were studied among 30 obese (BMI = 41 ± 8 kg/m2) and 35 nonobese (BMI = 24 ± 3 kg/m2) individuals. Platelet activation status was evaluated by flow cytometry using specific antibodies against the activated platelet membrane glycoprotein IIb/IIIa, p-selectin (CD-62 p), and binding of Annexin-V to platelet anionic phospholipids. Results. Overweight, obese, and morbidly obese females had significantly elevated platelet counts (P<.0001) compared with normal-weight females. No significant elevation of platelet counts was observed in the male subgroups. A significant age adjusted correlation between BMI and platelet counts (P<.0001) was found among females. This correlation was attenuated (P=.001) after adjustment for hs-CRP concentrations. The flow cytometry analysis of platelets showed no significant differences in activation marker expression between nonobese and obese individuals. Discussion. Obesity may be associated with elevated platelet counts in females with chronic inflammation. Obesity is not associated with increased platelet activation.Dorit Samocha-Bonet, Dan Justo, Ori Rogowski, Nili Saar, Subchi Abu-Abeid, Galina Shenkerman, Itzhak Shapira, Shlomo Berliner, and Aaron Tomer© 2008, Hindawi Publishing Corporation. All rights reserved.The Importance of Fever as a Predictive Symptom for the Potency of Host's Monocytes to Release Pro- and Anti-Inflammatory Mediatorshttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/450196Objective. To clarify whether time lapsing from advent of fever as a first sign of sepsis may be indicative of the potency of monocytes for the release of pro- and anti-inflammatory mediators. Methods. Monocytes were isolated from blood of 51 septic patients and 9 healthy donors. Monocytes were incubated in the absence and presence of patients' serum and concentrations of tumour necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-10, and malondialdehyde (MDA) were estimated in supernatants. Patients were divided into three groups: group A: <12 hours; group B: 12–24 hours, and group C: >24 hours between initiation of fever and blood sampling. Results. TNFα of supernatants of groups B and C was higher than controls, as also were IL-6 of A and C, IL-10 of A and B, and MDA of A. IL-6 of group A was increased after addition of patients serum. A negative correlation was found between time from initiation of symptoms and IL-6 of monocyte supernatants incubated in the presence of patients serum. Median IL-6 of survivors was higher than nonsurvivors. Conclusion. Monocytes are potent for the release of pro- and anti-inflammatory mediators within the first 24 hours upon advent of fever related to sepsis; serum stimulates further release of IL-6 within the first 12 hours.Magdalini Kyriakopoulou, Anastasia Antonopoulou, Maria Raftogiannis, Fotini Baziaka, Thomas Tsaganos, Kyriaki Kanellakopoulou, and Evangelos J. Giamarellos-Bourboulis© 2008, Hindawi Publishing Corporation. All rights reserved.Comparison of C-Reactive Protein and Serum Amyloid A Protein in Septic Shock Patientshttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/631414Septic shock is a severe inflammatory state caused by an infectious agent. Our purpose was to investigate serum amyloid A (SAA) protein and C-reactive protein (CRP) as inflammatory markers of septic shock patients. Here we evaluate 29 patients in postoperative period, with septic shock, in a prospective study developed in a surgical intensive care unit. All eligible patients were monitored over a 7-day period by sequential organ failure assessment (SOFA) score, daily CRP, SAA, and lactate measurements. CRP and SAA strongly correlated up to the fifth day of observation but were not good predictors of mortality in septic shock.Domingos Dias Cicarelli, Joaquim Edson Vieira, and Fábio Ely Martins Benseñor© 2008, Hindawi Publishing Corporation. All rights reserved.Myeloperoxidase: A New Biomarker of Inflammation in Ischemic Heart Disease and Acute Coronary Syndromeshttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/135625Myeloperoxidase (MPO) is an enzyme stored in azurophilic granules of polymorphonuclear neutrophils and macrophages and released into extracellular fluid in the setting of inflammatory process. The observation that myeloperoxidase is involved in oxidative stress and inflammation has been a leading factor to study myeloperoxidase as a possible marker of plaque instability and a useful clinical tool in the evaluation of patients with coronary heart disease. The purpose of this review is to provide an overview of the pathophysiological, analytical, and clinical characteristics of MPO and to summarize the state of art about the possible clinical use of MPO as a marker for diagnosis and risk stratification of patients with acute coronary syndrome (ACS).Valentina Loria, Ilaria Dato, Francesca Graziani, and Luigi M. Biasucci© 2008, Hindawi Publishing Corporation. All rights reserved.COX-2 Gene Promoter Polymorphism and Coronary Artery Disease in Middle-Aged Men: The Helsinki Sudden Death Studyhttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/289453Cyclooxygenase (COX) catalyzes formation of prostaglandins that contribute to the inflammation in atherosclerosis. Our objective was to study whether the functional C variant of the −765G→C polymorphism in the human COX-2 gene associates with the severity of coronary atherosclerosis measured at the coronary artery level. The Helsinki sudden death study autopsy material (n = 300) comprised of Finnish men who died suddenly. The area of atherosclerotic lesions in the coronary arteries was quantitated, and coronary narrowing was measured. The occurrence of myocardial infarction (MI) was assessed. Genotyping was by restriction endonuclease analysis. Men carrying the minor C allele had larger areas of complicated lesions (P = .024) and a higher number of coronary arteries that had over 50% stenosis (P = .036) compared to men representing the common GG genotype. The COX-2 polymorphism was not associated with MI. Our data suggest that COX-2 may be involved in plaque growth.KatiH. Huuskonen, TarjaA. Kunnas, MinnaM. Tanner, Jussi Mikkelsson, Erkki Ilveskoski, PekkaJ. Karhunen, and SeppoT. Nikkari© 2008, Hindawi Publishing Corporation. All rights reserved.Early Expression of FcγRI (CD64) on Monocytes of Cardiac Surgical Patients and Higher Density of Monocyte Anti-Inflammatory Scavenger CD163 Receptor in “On-Pump” Patientshttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/235461Objective. Activation of innate immunity cells is inseparably linked to cardiac surgical operation. The aim of this study was to assess the kinetics in the expression of receptor for Fc part of IgG, FcγRI (CD64), and scavenger receptor CD163 on peripheral blood cells of cardiac surgical patients and to examine the effect of cardiac bypass as a separable influence on the systemic acute inflammatory response. Methods. Forty patients, twenty in each group, were randomly assigned to CABG surgery performed either with “on-pump” or without “off-pump” cardiopulmonary bypass. Standardized quantitative flow cytometry method was used to determine the expression of surface markers. Results. The density of CD64 molecule on monocytes reached maximum on the 1st postoperative day (P<.001) whereas the peak for CD64 molecule expression on granulocytes was postponed to the 3rd postoperative day (P<.001). The expression of CD163 scavenger molecule on monocytes reached maximum on the 1st postoperative day (P<.001). The density of CD163 molecule on monocytes on the 1st postoperative day is significantly higher in “on-pump” patients in comparison with “off-pump” patients (P<.001). Conclusion. In cardiac surgical patients the expression of activation marker FcγR1 (CD64) on monocytes is increased earlier in comparison with granulocytes in both “on-pump” and “off-pump” patients. The expression of scavenger molecule CD163 on monocytes is significantly higher in “on-pump” patients.Martina Kolackova, Manuela Kudlova, Pavel Kunes, Vladimir Lonsky, Jiri Mandak, Ctirad Andrys, Karolina Jankovicova, and Jan Krejsek© 2008, Hindawi Publishing Corporation. All rights reserved.Tumor Necrosis Factor-Alpha in Peripical Tissue Exudates of Teeth with Apical Periodontitishttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2007/69416Aim. The aim of this study was to determine tumor necrosis factor-alpha (TNF-α) levels in periapical exudates and to evaluate their relationship with radiological findings. Methodology. Periapical exudates were collected from root canals of 60 single-rooted teeth using absorbent paper points. TNF-α levels were determined by enzyme-linked immunosorbent assays. The samples were divided into three groups according to the periapical radiolucent area. Results. Nonparametric Kruskal-Wallis test revealed significant differences between TNF-α concentrations in control group (40, 57±28, 15 pg/mL) and group with larger radiolucent areas (2365, 79±582, 95 pg/mL), as well as between control and canals with small radiolucent areas (507, 66±278, 97) (P<.05). Conclusions. The levels of TNF-α increase significantly in teeth with periapical pathosis, from smaller to bigger lesions. This research and its results have shown that objective analysis of the TNF-α levels enables establishment of a relationship between different concentrations of TNF-α and different radiological changes.Sonja Pezelj-Ribarić, Karolina Magašić, Jelena Prpić, Ivana Miletić, and Zoran Karlović© 2008, Hindawi Publishing Corporation. All rights reserved.Serum IL-1β, IL-6, IL-8, and TNF-α Levels in Early Diagnosis and Management of Neonatal Sepsishttp://www.hindawi.com/GetArticle.aspx?doi=10.1155/2007/31397Aim. To determine serum IL-1β, IL-6, IL-8, and TNF-α levels in neonatal sepsis at the time of diagnosis and after therapy, and to show the meaningful on the follow up. Methods. This prospective study was performed on newborns who were hospitalized for neonatal sepsis and who were classified as culture-proven sepsis (n=12), as culture-negative sepsis (n=21), and as healthy newborns (n=17). Results. At the time of diagnosis, serum IL-1β, IL-6, IL-8, and TNF-α levels of culture-proven sepsis were significantly higher than those of the control groups (P<.05). At the time of diagnosis, IL-1β, IL-6, IL-8, and TNF-α levels of culture-proven sepsis and culture-negative sepsis were significantly higher than levels at the seventh day after antibiotic treatment. Conclusion. Serum IL-1β, IL-6, IL-8, and TNF-α are mediators of inflammation and can be used at the diagnosis and at the evaluation of the therapeutic efficiency in neonatal sepsis.A. Nese Citak Kurt, A. Denizmen Aygun, Ahmet Godekmerdan, Abdullah Kurt, Yasar Dogan, and Erdal Yilmaz© 2008, Hindawi Publishing Corporation. All rights reserved.Recent Developments in 1,3-β-Glucan Biology: Proceedings of the 5th Glucan Symposium (Tokyo, December 8, 2006)http://www.hindawi.com/GetArticle.aspx?doi=10.1155/2007/79648 Rylander© 2008, Hindawi Publishing Corporation. All rights reserved.