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Increased Inflammation (increased + inflammation)
Selected AbstractsEffect of raisin consumption on oxidative stress and inflammation in obesityDIABETES OBESITY & METABOLISM, Issue 11 2008J. W. Rankin Aim:, Oxidative stress can initiate increased inflammation that elevates risk for cardiovascular disease. The objective of this study was to determine the effects of daily consumption of raisins on markers of oxidative stress, inflammation and endothelial activation in response to an acute high-fat meal in overweight individuals. Methods:, Seventeen overweight men and women consumed 90 g raisins or isocaloric placebo (264 kcal/day) for 14 days in a randomized, crossover design while following a low-flavonoid diet. The oxidative [urinary 8-iso-prostaglandin-F2, (8-epi PGF2,) and serum oxygen radical absorbance capacity (ORAC)], inflammatory (serum C-reactive protein and interleukin-6), endothelial (serum soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1, sVCAM-1) and metabolic [free fatty acids (FFAs), triacylglycerol, glucose and insulin] response to four high-fat (53%) meals was tested pre- and postintervention. Results:, Urinary 8-epi PGF2, decreased (,22%) and fasting ORAC increased (+3%) after both interventions combined. Fasting protein-free ORAC was modestly (+3.5%) higher during the raisin than the placebo intervention. Neither the meals nor the raisins consistently induced fasted markers of inflammation or endothelial dysfunction. Gender influenced postprandial metabolic responses in that males responded with higher serum FFAs, sVCAM-1 and glucose compared with females. Conclusions:, Serum antioxidant capacity was modestly increased by daily raisin consumption, but this did not alter fasted or postprandial inflammatory response in these relatively healthy but overweight individuals. Providing all food in regular pattern reduced measures of oxidative stress. [source] Disease-specific Helicobacter pylori Virulence Factors: The Unfulfilled PromiseHELICOBACTER, Issue S1 2000David Y. Graham A number of putative virulence factors for Helicobacter pylori have been identified including cagA, vacA and iceA. The criteria for a true virulence factor includes meeting the tests of biologically plausibility with the associations being both experimentally and epidemiologically consistent. Although disease-specific associations have been hypothesized/claimed, there are now sufficient data to conclusively state that none of these putative virulence factors have disease specificity. CagA has been claimed to be associated with increased mucosal IL-8 and inflammation, increased density of H. pylori in the antrum, duodenal ulcer (DU), gastric cancer, and protection against Barrett's cancer. Only the increase in IL-8/inflammation is direct and substantiated. Different H. pylori strains with functional cag pathogenicity islands do not vary in virulance as it has been shown that mucosal IL-8 levels are proportional to the number of cagA +H. pylori independent of the disease from which the H. pylori were obtained. It is now known that the density of either cagA + and cagA,H. pylori in the antrum of patients with H. pylori gastritis is the same. In contrast, the mean density of H. pylori in the antrum in DU is greater than in the antrum of patients with H. pylori gastritis. Of interest, the density of H. pylori is higher in the corpus of patients with H. pylori gastritis than those with DU, suggesting that acid secretion plays a critical role in these phenomena. The presence of a functional cag pathogenicity island increases inflammation and it is likely that any factor that results in an increase in inflammation also increases the risk of a symptomatic outcome. Nevertheless, the presence of a functional cag pathogenicity island has no predictive value for the presence, or the future development of a clinically significant outcome. The hypothesis that iceA has disease specificity has not been confirmed and there is currently no known biological or epidemiological evidence for a role for iceA as a virulence factor in H. pylori -related disease. The claim that vacA genotyping might prove clinically useful, e.g. to predict presentation such as duodenal ulcer, has been proven wrong. Analysis of the worldwide data show that vacA genotype s1 is actually a surrogate for the cag pathogenicity island. There is now evidence to suggest that virulence is a host-dependent factor. The pattern of gastritis has withstood the test of time for its relation to different H. pylori -related diseases (e.g. antral predominant gastritis with duodenal ulcer disease). The primary factors responsible for the different patterns of gastritis in response to an H. pylori infection are environmental (e.g. diet), with the H. pylori strain playing a lesser role. Future studies should work to eliminate potential bias before claiming disease associations. Controls must exclude regional or geographic associations related to the common strain circulation and not to the outcome. The authors must also control for both the presence of the factor and for the disease association. The study should be sufficiently large and employ different diseases and ethnic groups for the results to be robust. The findings in the initial sample (data derived hypothesis) should be tested in a new group (hypothesis testing), preferably from another area, before making claims. Finally, it is important to ask whether the results are actually a surrogate for another marker (e.g. vacA s1 for cagA) masquerading for a new finding. Only the cag pathogenicity island has passed the tests of biological plausibility (increased inflammation) and experimental and epidemiological consistency. [source] Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney diseaseJOURNAL OF INTERNAL MEDICINE, Issue 6 2007J. J. Carrero Abstract., Carrero JJ, Qureshi AR, Axelsson J, Yilmaz MI, Rehnmark S, Witt MR, Bárány P, Heimbürger O, Suliman ME, Alvestrand A, Lindholm B, Stenvinkel P (Karolinska Institutet, Stockholm; and Karo Bio AB, Novum, Huddinge; Sweden). Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease. J Intern Med 2007; 262: 690,701. Objectives., In this study, we explore the associations of decreased thyroid hormone levels with inflammation, wasting and survival in biochemically euthyroid patients with end-stage renal disease (ESRD). Design., After exclusion of 23 patients with thyroid-stimulating hormone (TSH) values outside the normal range (0.1,4.5 mIU L,1), 187 clinically and biochemically euthyroid incident ESRD stage 5 patients starting dialysis were followed for a median of 20 (range 1,60) months. Measurements of total and free forms of thyroid hormones, s-albumin, hs-CRP, interleukin (IL)-6, vascular adhesion molecule (VCAM)-1 and insulin-like growth factor 1 (IGF-1) were performed at baseline. Results., In this population, 17 out of 210 patients (8%) were defined as subclinically hypothyroid. Multivariate analysis, according to receiver operating characteristic (ROC) curves, showed that mortality was best predicted by total triiodothyronine (T3). When using the cut-off levels derived from ROC, low T3 levels were associated with increased inflammation (higher hs-CRP, IL-6 and VCAM-1) and lower concentration of both s-albumin and IGF-1. Finally, low T3 but not low free triiodothyronine was associated with worse all-cause (Likelihood ratio = 45.4; P < 0.0001) and cardiovascular mortality (Likelihood ratio = 47.8; P < 0.0001) after adjustment for confounding factors. Conclusion., This study showed that low T3 levels are independent predictors of all-cause and also cardiovascular disease mortality in biochemically euthyroid patients, perhaps due to an intimate association with inflammation. Based on these results, the use of T3 levels in studies assessing the relationship between thyroid dysfunction and mortality risk is recommended. [source] Noradrenergic depletion potentiates ,-amyloid induced cortical inflammation: implications for Alzheimer's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 2002D. L. Feinstein Degeneration of locus ceruleus (LC) neurons and reduced levels of noradrenaline (NA) in LC projection areas is a well known feature of Alzheimer's disease (AD); however, the consequences of those losses are not clear. Since inflammatory mediators contribute to AD pathogenesis, and since NA can suppress inflammatory gene expression, we tested if LC loss influenced brain inflammatory gene expression elicited by amyloid , (A,). Adult rats were injected with the selective neurotoxin DSP4 to induce LC death, and subsequently injected in cortex with A, (aggregated 1,42 peptide). DSP4-treatment potentiated the A,-dependent induction of inflammatory nitric oxide synthase (iNOS), IL-1, and IL6 expression compared to control animals. In contrast, the induction of cyclooxygenase-2 expression was not modified by DSP4-treatment. In control animals, injection of A, induced iNOS primarily in microglial cells, while in DSP4-treated animals iNOS was localized to neurons, as is observed in AD brains. Injection of A, increased IL-1, expression initially in microglia, and at later times in astrocytes, and expression levels were greater in DSP4 treated animals than controls. The potentiating effects of DSP4-treatment on iNOS and IL-1, expression were attenuated by coinjection with NA or the ,-adrenergic receptor agonist isoproterenol. These data demonstrate that LC loss and NA depletion augment inflammatory responses to A,, and suggest that LC loss in AD is permissive for increased inflammation and neuronal cell death. [source] Progressive Renal Vascular Proliferation and Injury in Obese Zucker RatsMICROCIRCULATION, Issue 4 2010RADU ILIESCU Microcirculation (2010) 17, 250,258. doi: 10.1111/j.1549-8719.2010.00020.x Abstract Objective:, Obesity, an independent risk factor for chronic kidney disease, may induce renal injury by promoting inflammation. Inflammatory cytokines can induce neovascularization in different organs, including the kidneys. However, whether obesity triggers renal neovascularization and, if so, its effect on renal function has never been investigated. Methods:, Blood pressure, proteinuria, and glomerular filtration rate (GFR) were measured in vivo. Renal microvascular (MV) architecture was studied by 3D micro-CT in lean and obese Zucker rats (LZR and OZR, n = 7/group) at 12, 22, and 32 weeks of age. Renal inflammation was assessed by quantifying interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and ED-1 expression, as renal fibrosis in trichrome-stained cross-sections. Results:, Mild inflammation and lower GFR was only observed in younger OZR, without renal fibrosis or changes in MV density. Interestingly, renal MV density increased in OZR at 32 weeks of age, accompanied by pronounced increase in renal IL-6 and TNF-alpha, ED-1+ cells, proteinuria, decreased GFR, and fibrosis. Conclusions:, This study shows increased renal cortical vascularization in experimental obesity, suggesting neovascularization as an evolving process as obesity progresses. Increased renal vascularization, possibly triggered by inflammation, may reflect an initially compensatory mechanism in obesity. However, increased inflammation and inflammatory-induced neovascularization may further promote renal injury as obesity advances. [source] High frequency of gastroduodenal cytomegalovirus infection in liver transplant patients,APMIS, Issue 2 2008LEENA HALME The prevalence and significance of cytomegalovirus (CMV) detected in biopsy specimens from the gastroduodenal mucosa of liver transplant patients, patients with chronic or acute liver failure and immunocompetent patients with dyspeptic symptoms were evaluated. 80 liver transplant patients with upper gastrointestinal symptoms, 132 patients with chronic and 25 with acute liver failure, and 33 immunocompetent, dyspeptic patients underwent oesophagogastroduodenoscopies, with biopsies from the duodenum and stomach. CMV was demonstrated by immunohistochemistry in frozen sections, using a monoclonal antibody against CMV-specific antigens (pp65 matrix protein), and in paraffin sections by a monoclonal antibody against delayed early protein (p52). 71% of the liver transplant patients, 45% of the patients with chronic liver disease, 20% with acute liver failure, and 45% of the immunocompetent, dyspeptic patients had CMV-positive findings in the gastroduodenal mucosa (liver transplant patients vs other groups, p<0.01). Histopathological findings in CMV-positive samples were focal inflammation, including increased inflammation of the lamina propria, infiltrating leukocytes intra-epithelially, regenerative changes in the epithelial cells and inclusion bodies. In conclusion, CMV-positive cells and inclusions are often found in the gastroduodenal mucosa of liver transplant patients, as well as in patients suffering from chronic liver disease or even in otherwise healthy patients with dyspeptic symptoms. [source] Increased expression of interleukin-7 in labial salivary glands of patients with primary Sjögren's syndrome correlates with increased inflammationARTHRITIS & RHEUMATISM, Issue 4 2010A. Bikker Objective To study the expression levels and immunostimulatory capacities of interleukin-7 (IL-7) in primary Sjögren's syndrome. Methods Labial salivary gland (LSG) IL-7 expression was determined by immunohistochemistry, using a quantitative scoring system, in 30 patients with sicca syndrome: 15 patients with primary Sjögren's syndrome (SS) and 15 patients with non-SS sicca syndrome. The correlation of IL-7 expression in LSGs with parameters of local and peripheral disease was studied, and serum and salivary IL-7 levels were determined. Additionally, the effects of IL-7 on cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with primary SS were determined in vitro by Luminex multicytokine assay and compared with the effects in control subjects. Results The expression of IL-7 in LSGs was higher in patients with primary SS compared with that in patients with non-SS sicca syndrome. IL-7 was observed primarily in the vicinity of lymphocytic infiltrates. Salivary IL-7 levels in patients with primary SS were higher than those in control subjects. In all 30 patients with sicca syndrome, IL-7 expression in LSGs correlated with parameters of both local and peripheral disease. Furthermore, IL-7 stimulated T cell,attracting and T cell,differentiating cytokines (monokine induced by interferon-, [IFN,], IFN,-inducible 10-kd protein, IL-12, and IL-15), as well as Th1 (IFN,), Th2 (IL-4), Th17 (IL-17A), proinflammatory (tumor necrosis factor , and IL-1,), and regulatory (IL-10 and IL-13) cytokine production by PBMCs. All of these cytokines were previously shown to be associated with primary SS. The IL-7,induced increase in IL-10 production in patients with primary SS was reduced compared with that in control subjects. Conclusion The correlation between LSG IL-7 expression and (local) disease parameters in primary SS as well as the IL-7,mediated induction of inflammatory cytokines indicate that IL-7 might contribute to the immunopathology of primary SS. [source] Bim,Bcl-2 homology 3 mimetic therapy is effective at suppressing inflammatory arthritis through the activation of myeloid cell apoptosisARTHRITIS & RHEUMATISM, Issue 2 2010John C. Scatizzi Objective Rheumatoid arthritis (RA) is a destructive autoimmune disease characterized by an increased inflammation in the joint. Therapies that activate the apoptotic cascade may have potential for use in RA; however, few therapeutic agents fit this category. The purpose of this study was to examine the potential of Bim, an agent that mimics the action of Bcl-2 homology 3 (BH3) domain,only proteins that have shown success in preclinical studies of cancer, in the treatment of autoimmune disease. Methods Synovial tissues from RA and osteoarthritis patients were analyzed for the expression of Bim and CD68 using immunohistochemistry. Macrophages from Bim,/, mice were examined for their response to lipopolysaccharide (LPS) using flow cytometry, real-time polymerase chain reaction analysis, enzyme-linked immunosorbent assay, and immunoblotting. Bim,/, mice were stimulated with thioglycollate or LPS and examined for macrophage activation and cytokine production. Experimental arthritis was induced using the K/BxN serum,transfer model. A mimetic peptide corresponding to the BH3 domain of Bim (TAT-BH3) was administered as a prophylactic agent and as a therapeutic agent. Edema of the ankles and histopathologic analysis of ankle tissue sections were used to determine the severity of arthritis, its cellular composition, and the degree of apoptosis. Results The expression of Bim was reduced in RA synovial tissue as compared with controls, particularly in macrophages. Bim,/, macrophages displayed elevated expression of markers of inflammation and secreted more interleukin-1, following stimulation with LPS or thioglycollate. TAT-BH3 ameliorated arthritis development, reduced the number of myeloid cells in the joint, and enhanced apoptosis without inducing cytotoxicity. Conclusion These data demonstrate that BH3 mimetic therapy may have significant potential for the treatment of RA. [source] Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2009GG Donders Introduction, Abnormal vaginal flora (AVF) before 14 gestational weeks is a risk factor for preterm birth (PTB). The presence of aerobic microorganisms and an inflammatory response in the vagina may also be important risk factors. Aim, The primary aim of the study was to investigate the differential influences of AVF, full and partial bacterial vaginosis, and aerobic vaginitis in the first trimester on PTB rate. The secondary aim was to elucidate why treatment with metronidazole has not been found to be beneficial in previous studies. Setting, Unselected women with low-risk pregnancies attending the prenatal unit of the Heilig Hart General Hospital in Tienen, Belgium, were included in the study. Materials and methods, At the first prenatal visit, 1026 women were invited to undergo sampling of the vaginal fluid for wet mount microscopy and culture, of whom 759 were fully evaluable. Abnormal vaginal flora (AVF; disappearance of lactobacilli), bacterial vaginosis (BV), aerobic vaginitis (AV), increased inflammation (more than ten leucocytes per epithelial cell) and vaginal colonisation with Candida (CV) were scored according to standardised definitions. Partial BV was defined as patchy streaks of BV flora or sporadic clue cells mixed with other flora, and full BV as a granular anaerobic-type flora or more than 20% clue cells. Vaginal fluid was cultured for aerobic bacteria, Mycoplasma hominis and Ureaplasma urealyticum. Outcome was recorded as miscarriage ,13 weeks + 6 days [early miscarriage (EM), n = 8 (1.1%)], between 14 + 0 and 24 weeks + 6 days [late miscarriage (LM), n = 7 (0.9%)], delivery or miscarriage ,34 weeks + 6 days n = 29 (3.8%)], ,36 weeks + 6 days n = 70 (9.2%)]. PTB between 25 + 0 and 36 weeks + 6 days was further divided in severe PTB (SPTB, 25 + 0 to 34 weeks + 6 days) and mild PTB (MPTB, 35 + 0 to 36 weeks + 6 days). Results, Women without abnormalities of the vaginal flora in the first trimester had a 75% lower risk of delivery before 35 weeks compared with women with AVF [odds ratio (OR) 0.26; 95% confidence interval (CI) 0.12,0.56]. The absence of lactobacilli (AVF) was associated with increased risks of PTB (OR 2.4; 95% CI 1.2,4.8), EPTB (OR 6.2; 95% CI 2.7,14) and miscarriage (OR 4.9; 95% CI 1.4,17). BV was associated with increased risks of PTB (OR 2.4; 95% CI 1.1,4.7), EPTB (OR 5.3; 95% CI 2.1,12.9) and miscarriage (OR 6.6; 95% CI 2.1,20.9) and coccoid AV was associated with increased risks of EPTB (OR 3.2; 95% CI 1.2,9.1) and miscarriage (OR 5.2; 95% CI 1.5,17). In women with BV, partial BV had a detrimental effect on the risk of PTB for all gestational ages, but full BV did not. Preterm deliveries later than 24 weeks+ 6 days were more frequent when M. hominis was present (EPTB OR 13.3; 95% CI 3.2,55). Discussion, Bacterial vaginosis, AV and AVF are associated with PTB, especially LM and severe PTB between 25 and 35 weeks. The absence of lactobacilli (AVF), partial BV and M. hominis, but not full BV, were associated with an increased risk of preterm delivery after 24 weeks+ 6 days. As metronidazole effectively treats full BV, but is ineffective against other forms of AVF, the present data may help to explain why its use to prevent PTB has not been successful in most studies. [source] Effects of 4 months of smoking in mice with ovalbumin-induced airway inflammationCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2007B. N. Melgert Summary Background The effects of smoking on asthma pathogenesis are complex and not well studied. We have shown recently that 3 weeks of smoking attenuates ovalbumin (OVA)-induced airway inflammation in mice and that 4,6 months of smoking induces emphysema in mice without airway inflammation. Effects of combined long-term smoking and OVA exposure have not been investigated so far. Objective To study whether long-term smoking affects progression of allergic airway inflammation and/or enhances the development of emphysema in mice. Methods Mice were sensitized to OVA and challenged with saline or OVA aerosols for 6 months. From 2 months onwards, mice were also exposed to air or smoke. Lung tissue was analysed for extent of inflammation, emphysema, remodelling and for cytokine levels, and serum for OVA-specific IgE levels. Results Chronic OVA exposure of 6 months resulted in a T helper type 2 (Th2)-type inflammation with increased levels of IL-4, IL-5, IL-6 and infiltration of eosinophils, CD4+ T cells, macrophages and plasma cells. Smoking induced a Th17-type of airway inflammation, characterized by neutrophils, macrophages, B cells and increased levels of IL-17, IL-6, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1. Concomittant smoking and OVA exposure resulted in inflammation similar to OVA exposure alone. OVA exposure increased IgE levels compared with saline exposure, and smoking did not further increase these levels. Conclusion We did not find evidence for increased inflammation, IgE levels or emphysema in mice with allergic airway inflammation after 4 months of smoking compared with non-smoking. However, a 4-month exposure to smoke alone did enhance neutrophilic airway inflammation characterized by high pulmonary IL-17 levels. A Th2 inflammatory environment due to OVA exposure may be one explanation as to why no further detrimental effects of smoking on allergic airway inflammation were found. [source] | ||||||||||