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Chronic Inflammatory Conditions (chronic + inflammatory_condition)
Selected AbstractsInterferon regulatory factor-3 activation, hepatic interferon-stimulated gene expression, and immune cell infiltration in hepatitis C virus patients,HEPATOLOGY, Issue 3 2008Daryl T.-Y. Interferon regulatory factor-3 (IRF-3) activation directs ,/, interferon production and interferon-stimulated gene (ISG) expression, which limits virus infection. Here, we examined the distribution of hepatitis C virus (HCV) nonstructural 3 protein, the status of IRF-3 activation, and expression of IRF-3 target genes and ISGs during asynchronous HCV infection in vitro and in liver biopsies from patients with chronic HCV infection, using confocal microscopy and functional genomics approaches. In general, asynchronous infection with HCV stimulated a low-frequency and transient IRF-3 activation within responsive cells in vitro that was associated with cell-to-cell virus spread. Similarly, a subset of HCV patients exhibited the nuclear, active form of IRF-3 in hepatocytes and an associated increase in IRF-3 target gene expression in hepatic tissue. Moreover, ISG expression profiles formed disease-specific clusters for HCV and control nonalcoholic fatty liver disease patients, with increased ISG expression among the HCV patients. We identified the presence of T cell and plasmacytoid dendritic cell infiltrates within all biopsy specimens, suggesting they could be a source of hepatic interferon in the setting of hepatitis C and chronic inflammatory condition. Conclusion: These results indicate that HCV can transiently trigger IRF-3 activation during virus spread and that in chronic HCV, IRF-3 activation within infected hepatocytes occurs but is limited. (HEPATOLOGY 2007.) [source] Abnormal Pap smears in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 8 2008Sunanda Kane MD Abstract Inflammatory bowel disease (IBD) is a chronic inflammatory condition that is frequently treated with immunomodulators. Previous work has demonstrated an increased risk for abnormal cervical cytology in women treated with chronic immunosuppression, due mainly to human papillomavirus. This review summarizes the data known for this relationship in women with IBD, and management strategies for patients found to have abnormal cervical cytology. (Inflamm Bowel Dis 2008) [source] Asthma and oral health: a reviewAUSTRALIAN DENTAL JOURNAL, Issue 2 2010MS Thomas Abstract Asthma is a chronic inflammatory condition that causes the airways to constrict and produce excess mucus, making breathing difficult. It is characterized by the obstruction of airflow which is variable over a short period of time. This condition is reversible, either spontaneously or can be controlled with the help of drugs. Asthma medication comprises bronchodilators, corticosteroids and anticholinergic drugs. Most of these drugs are inhaled using various forms of inhalers or nebulizers. The effect of these drugs on oral health is the subject of debate among dental practitioners. Patients taking asthma medication may be at risk of dental caries, dental erosion, periodontal diseases and oral candidiasis. Hence, patients with bronchial asthma on medication should receive special prophylactic attention. This article reviews the correlation between asthma and oral health, and suggests various measures to counter possible oral health problems related to asthma. [source] Clindamycin and rifampicin combination therapy for hidradenitis suppurativaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2006C.O. Mendonça Summary Background, Hidradenitis suppurativa (HS) is a chronic inflammatory condition affecting apocrine gland-bearing areas of the skin. There is currently no satisfactory treatment. Objectives, To assess the efficacy of a 10-week course of combination clindamycin 300 mg twice daily and rifampicin 300 mg twice daily in the treatment of HS. Methods, Patients who had received combination therapy with clindamycin and rifampicin for HS at one U.K. Dermatology Centre between the years 1998 and 2003 were identified from pharmacy records. Their records were analysed retrospectively. Results, Fourteen patients with HS had received treatment with combination therapy. Eight of these patients achieved remission and a further two achieved remission when minocycline was substituted for clindamycin. Four patients were unable to tolerate therapy. Conclusions, This small retrospective study indicates that combination therapy with clindamycin and rifampicin may be effective for HS. However, there is a need for a placebo-controlled trial. [source] Inhibition of caspase-dependent spontaneous apoptosis via a cAMP-protein kinase A dependent pathway in neutrophils from sickle cell disease patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2007Nicola Conran Summary Sickle cell disease (SCD) is a chronic inflammatory condition characterized by high leucocyte counts, altered cytokine levels and endothelial cell injury. As the removal of inflammatory cells by apoptosis is fundamental for the resolution of inflammation, we aimed to determine whether the leucocyte apoptotic process is altered in SCD. Neutrophils from SCD individuals showed an inhibition of spontaneous apoptosis when cultured in vitro, in the presence of autologous serum for 20 h. Intracellular cyclic adenosine monophosphate (cAMP) levels were approximately twofold increased in SCD neutrophils; possible cAMP-upregulating factors present in SCD serum include interleukin-8, granulocyte-macrophage colony-stimulating factor and prostaglandin. Accordingly, co-incubation of SCD neutrophils with KT5720, a cAMP-dependent protein kinase (PKA) inhibitor, abrogated increased SCD neutrophil survival. Caspase-3 activity was also significantly diminished in SCD neutrophils cultured for 16 h and this activity was restored when cells were co-incubated with KT5720. BIRC2 (encoding cellular inhibitor of apoptosis protein 1, cIAP1), MCL1 and BAX expression were unaltered in SCD neutrophils; however, BIRC3 (encoding the caspase inhibitor, cIAP2), was expressed at significantly higher levels. Thus, we report an inhibition of spontaneous SCD neutrophil apoptosis that appears to be mediated by upregulated cAMP-PKA signalling and decreased caspase activity. Increased neutrophil survival may have significant consequences in SCD; contributing to leucocytosis, tissue damage and exacerbation of the chronic inflammatory state. [source] How reliably can autoimmune hypophysitis be diagnosed without pituitary biopsyCLINICAL ENDOCRINOLOGY, Issue 1 2010Trevor A. Howlett Summary Autoimmune hypophysitis is a rare chronic inflammatory condition of the pituitary gland which typically presents with hypopituitarism and a pituitary mass. Cases involving anterior pituitary alone (65%) are six times more common in women, typically presenting during pregnancy or postpartum (57%). Anterior and posterior pituitary involvement (25%) are twice as common in women, and neurohypophysis alone (10%) occurs equally in both sexes. It has a prevalence of around 5 per million, an annual incidence of 1 in 7 to 9 million and in our experience represents the known or suspected cause of 0·5% of cases of hypopituitarism, <1% of pituitary masses and 2% of nonfunctioning macro lesions presenting to an endocrine clinic. However, ,missed' cases of autoimmune hypophysitis may be the aetiology of some other unexplained cases of hypopituitarism. Clinically, headache and visual disturbance are common. Anterior hypopituitarism shows a characteristic but atypical pattern of deficiency of ACTH followed by TSH, gonadotrophins and prolactin deficiency or hyperprolactinaemia. Eighteen percent of cases have evidence of another autoimmune condition. On magnetic resonance imaging (MRI), autoimmune hypophysitis is typically symmetrical and homogeneous with thickened but undisplaced stalk in contrast to typical findings with pituitary tumours. Ultimately, the histological diagnosis of autoimmune hypophysitis can only be confirmed by surgery but a presumptive diagnosis can often be made on the basis of a combination of context and clinical features, and pituitary biopsy is not always clinically necessary for effective clinical management of the patient. [source] Nitric oxide and p53 in cancer-prone chronic inflammation and oxyradical overload disease,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2004Julie E. Goodman Abstract Nitric oxide (NO·), which is generated under chronic inflammatory conditions that predispose individuals to cancer, has paradoxical effects. NO· can activate p53, which can result in anti-carcinogenic effects, or it can be mutagenic and increase cancer risk. We explored the mechanisms by which NO· induced p53 activation in vitro and found that NO· induced p53 accumulation and phosphorylation, particularly at ser-15, via ATM and ATR kinases, which then led to cell cycle arrest at G2/M. We next examined proteins in these pathways in both inflamed and normal human colon tissue. Inducible nitric oxide synthase (iNOS) levels and p53-P-ser15 levels were positively correlated with the degree of inflammation and with each other. Additionally, the p53 targets, HDM-2 and p21 (WAF1), were present in ulcerative colitis (UC) colon, but undetectable in normal colon, consistent with activated p53. We also found higher p53 mutant frequencies of both G:C , A:T transitions at the CpG site of codon 248 and C:G , T:A transitions at codon 247 in lesional colon tissue from UC cases versus nonlesional tissue from these cases or colon tissue from normal adult controls. Consistent with nitrosative stress and the deamination of 5-methylcytosine, p53 mutations were also detected in sporadic colon cancer tissue and were associated with iNOS activity in these tissues. These studies identified a potential mechanistic link between NO· and p53 in UC and sporadic colon cancer. Environ. Mol. Mutagen. 44:3,9, 2004. Published 2004 Wiley-Liss, Inc. [source] Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysinINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Hao-Wei Wang Abstract Dihydrodiol dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily (AKR1C1,AKR1C4), which plays central roles in the metabolism of steroid hormone, prostaglandin and xenobiotics. We have previously detected overexpression of DDH as an indicator of poor prognosis and chemoresistance in human non-small lung cancer (NSCLC). We also found DDH expression to be closely related to chronic inflammatory conditions. The aim of this study was to investigate the links between inflammation, DDH expression and drug resistance in NSCLC cells. We showed that pro-inflammatory mediators including interleukin-6 (IL-6) could induce AKR1C1/1C2 expression in NSCLC cells and increase cellular resistance to cisplatin and adriamycin. This effect was nullified by Safingol, a protein kinase C inhibitor. Moreover, the expression of AKR1C1/1C2 was inversely correlated to NBS1 and apoptosis-inducing factor (AIF). We also showed that IL-6-induced AKR1C1/1C2 expression and drug resistance were inhibited by wogonin and chrysin, which are major flavonoids in Scutellaria baicalensis, a widely used traditional Chinese and Japanese medicine. In conclusion, this study demonstrated novel links of pro-inflammatory signals, AKR1C1/1C2 expression and drug resistance in NSCLC. The protein kinase C pathway may play an important role in this process. Overexpression of AKR1C1/1C2 may serve as a marker of chemoresistance. Further studies are warranted to evaluate wogonin and chrysin as a potential adjuvant therapy for drug-resistant NSCLC, especially for those with AKR1C1/1C2 overexpression. © 2007 Wiley-Liss, Inc. [source] Inter-relationships between rheumatoid arthritis and periodontal diseaseJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2003A review Abstract This review considers the considerable similarities between periodontal disease and rheumatoid arthritis (RA). While the etiology of these two diseases may differ, the underlying pathogenic mechanisms are remarkably similar and it is possible that individuals manifesting both periodontitis and RA may suffer from a unifying underlying systemic dysregulation of the inflammatory response. In light of these findings, the implications for the use of disease-modifying medications in the management of these two chronic inflammatory conditions is apparent. Further longitudinal studies and medication-based intervention studies are required to determine just how closely these two conditions are allied. Zusammenfassung Diese Übersicht berücksichtigt die beträchtlichen Ähnlichkeiten zwischen einer Parodontalerkrankung und der rheumatoiden Arthritis. Während die Ätiologie dieser zwei Erkrankungen sich unterscheiden kann, sind die zugrundeliegenden Pathogenitätsmechanismen bemer-kenswert ähnlich. Und es ist möglich, dass Personen bei denen sich sowohl eine Parodontitis als auch eine rheumatoide Arthritis manifestiert hat, an einer verbindenden zugrundeliegenden systemischen Dysregulation der Entzündungsreaktion leiden könnten. Unter Berücksichtigung dieser Ergebnisse ist es offensichtlich, dass, bei der Beherrschung dieser zwei chronischen entzündlichen Zustände, die Verwendung von die Erkrankung modifizierenden Medikamenten, indiziert ist. Weitere Longitudinalstudien und Interventionsstudien mit Medikamenten sind notwendig, um zu bestimmen, wie nahe diese zwei Zustände verwandt sind. Résumé Cette revue considère les similarités considérables qui existent entre la maladie parodontale et l'arthrite rhumatoïde. Tandis que l'étiologie de ces deux maladies peut être différente, les mécanismes pathogéniques sous-jacents sont remarquablement semblables et il est possible que les individus avec arthrite rhumatoïde puissent souffrir d'une dérégularisation systémique sous-jacente unifiée de la réponse inflammatoire. A la lumière de ces découvertes, les implications de l'utilisation de médicaments modifiant la maladie dans le traitement de ces deux conditions inflammatoires chroniques est apparent. Davantage d'études longitudinales et d'études où il y a une intervention médicamenteuse sont requises pour déterminer le proportion de proximité de ces deux conditions. [source] Novel role of TGF-, in differential astrocyte-TIMP-1 regulation: Implications for HIV-1-dementia and neuroinflammationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2006Alok Dhar Abstract Astrocyte production of tissue inhibitor of metalloproteinase (TIMP)-1 is important in central nervous system (CNS) homeostasis and inflammatory diseases such as HIV-1-associated dementia (HAD). TIMPs and matrix metalloproteinases (MMPs) regulate the remodeling of the extracellular matrix. An imbalance between TIMPs and MMPs is associated with many pathologic conditions. Our recently published studies uniquely demonstrate that HAD patients have reduced levels of TIMP-1 in the brain. Astrocyte-TIMP-1 expression is differentially regulated in acute and chronic inflammatory conditions. In this and the adjoining report (Gardner et al., 2006), we investigate the mechanisms that may be involved in differential TIMP-1 regulation. One mechanism for TIMP-1 downregulation is the production of anti-inflammatory molecules, which can activate signaling pathways during chronic inflammation. We investigated the contribution of transforming growth factor (TGF)-signaling in astrocyte-MMP/TIMP-1-astrocyte regulation. TGF-,1 and ,2 levels were upregulated in HAD brain tissues. Co-stimulation of astrocytes with IL-1, and TGF-, mimicked the TIMP-1 downregulation observed with IL-1, chronic activation. Measurement of astrocyte-MMP protein levels showed that TGF-, combined with IL-1, increased MMP-2 and decreased proMMP-1 expression compared to IL-1, alone. We propose that one of the mechanisms involved in TIMP-1 downregulation may be through TGF-signaling in chronic immune activation. These studies show a novel extracellular regulatory loop in astrocyte-TIMP-1 regulation. © 2006 Wiley-Liss, Inc. [source] Pharmacological studies on Indian black tea (leaf variety) in acute and chronic inflammatory conditionsPHYTOTHERAPY RESEARCH, Issue 6 2008Dilip K. Roy Abstract Infusions of Indian black tea (BTI), when administered orally, produced significant inhibition of rat paw oedema, induced with carrageenin (pre and post treatment) and arachidonic acid. BTI was also found to inhibit peritoneal capillary permeability and caused a marked reduction of lipopolysaccharide induced PGE2 generation. In these models, the observed antioedema effect was similar to that of BW755C (a dual inhibitor of cyclooxygenase and 5-lipoxygenase enzymes). BTI was found to scavenge superoxide and hydroxyl radicals, and also protected rat erythrocytes from the damaging effects of hydrogen peroxide. In chronic studies, BTI inhibited granuloma formation along with the reduction of both lipid peroxidation and hydroxyproline content (in the granuloma tissue). Significant antiarthritic activity was observed with regular administration of BTI in the Freund's adjuvant induced model of arthritis. Chronic treatment with BTI (in arthritic rats) resulted in a decrease of paw diameter and tissue lipid peroxidation, along with a restoration of GSH, catalase and superoxide dismutase levels. Copyright © 2008 John Wiley & Sons, Ltd. [source] Cancer risk in patients with rheumatoid arthritis treated with anti,tumor necrosis factor , therapies: Does the risk change with the time since start of treatment?ARTHRITIS & RHEUMATISM, Issue 11 2009Johan Askling Objective To determine the short-term and medium-term risks of cancer in patients receiving anti,tumor necrosis factor , (anti-TNF,) therapies that have proven effective in the treatment of chronic inflammatory conditions. Methods By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received. Results During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86,1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed. Conclusion During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed. [source] Improvement of lipid profile is accompanied by atheroprotective alterations in high-density lipoprotein composition upon tumor necrosis factor blockade: A prospective cohort study in ankylosing spondylitisARTHRITIS & RHEUMATISM, Issue 5 2009I. C. van Eijk Objective Cardiovascular mortality is increased in ankylosing spondylitis (AS), and inflammation plays an important role. Inflammation deteriorates the lipid profile and alters high-density lipoprotein cholesterol (HDL-c) composition, reflected by increased concentrations of serum amyloid A (SAA) within the particle. Anti,tumor necrosis factor (anti-TNF) treatment may improve these parameters. We therefore undertook the present study to investigate the effects of etanercept on lipid profile and HDL composition in AS. Methods In 92 AS patients, lipid levels and their association with the inflammation markers C-reactive protein (CRP), erythrocyte sedimentation rate, and SAA were evaluated serially during 3 months of etanercept treatment. HDL composition and its relationship to inflammation markers was determined in a subgroup of patients, using surface-enhanced laser desorption/ionization time-of-flight analysis. Results With anti-TNF treatment, levels of all parameters of inflammation decreased significantly, whereas total cholesterol, HDL-c, and apolipoprotein A-I (Apo A-I) levels increased significantly. This resulted in a better total cholesterol:HDL-c ratio (from 3.9 to 3.7) (although the difference was not statistically significant), and an improved Apo B:Apo A-I ratio, which decreased by 7.5% over time (P = 0.008). In general, increases in levels of all lipid parameters were associated with reductions in inflammatory activity. In addition, SAA was present at high levels within HDL particles from AS patients with increased CRP levels and disappeared during treatment, in parallel with declining plasma levels of SAA. Conclusion Our results show for the first time that during anti-TNF therapy for AS, along with favorable changes in the lipid profile, HDL composition is actually altered whereby SAA disappears from the HDL particle, increasing its atheroprotective ability. These findings demonstrate the importance of understanding the role of functional characteristics of HDL-c in cardiovascular diseases related to chronic inflammatory conditions. [source] Extracellular matrix metabolites as potential biomarkers of disease activity in wound fluid: lessons learned from other inflammatory diseases?BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004R. Moseley Summary The new era of pharmacogenetics has identified a potential for individuals to receive customized treatments for a variety of disease states. For such individualized treatments to fulfil their potential, it will be essential for clinicians to be able to monitor disease activity, ideally in a rapid, noninvasive fashion. The accessibility of the skin offers much potential to develop noninvasive tests of metabolic and disease activity for clinical use. Impaired human wound healing in the skin is a chronic inflammatory disorder in which the development of such tests has considerable potential, aiding clinical decision making and monitoring responses to treatment. This review article discusses how studies in other human diseases have highlighted potential biochemical markers (biomarkers) of disease activity in secreted biofluids, as aids to determining disease and metabolic activity within tissues. Using, as examples, lessons learned in the study of disease activity and prognosis of other chronic inflammatory conditions, such as osteoarthritis and periodontal disease, this review highlights the potential of dermal extracellular matrix (ECM) components (collagens, proteoglycans, hyaluronan and glycoproteins) for such uses. The limitations of currently utilized techniques and the concept that analysis of ECM components in wound fluid may represent useful biomarkers of disease activity are also discussed. [source] The prediction of coronary atherosclerosis employing artificial neural networksCLINICAL CARDIOLOGY, Issue 6 2000Jacob George M.D. Abstract Background: Atherosclerosis is a complex histopathologic process that is analogous to chronic inflammatory conditions. Several factors have been shown to correlate with the extent of atherosclerosis. Whereas hypertension, obesity, hyperlipidemia, diabetes, smoking, and family history are all well documented, recent literature points to additional associated factors. Thus, antibodies to oxidized low-density lipoprotein (oxLDL), cytomegalovirus (CMV), Chlamydia pneumonia, Helicobacter pylori, as well as homocysteine and C-reactive protein (CRP) levels have all been implicated as independent markers of accelerated atherosclerosis. Hypothesis: In the current study we attempted to formulate a system by which to predict the extent of coronary atherosclerosis as assessed by angiographic vessel occlusion. Methods: The 81 patients were categorized as having single-, double-, triple-, or no vessel involvement. The clinical data concerning the "classic" risk factors were obtained from clinical records, and sera were drawn from the patients for determination of the various parameters that are thought to be associated with atherosclerosis. Results: Using four artificial neural networks, we have found the most effective parameters predictive of coronary vessel involvement were (in decreasing order of importance) antibodies to oxLDL, to cardiolipin, to CMV, to Chlamydia pneumonia, and to ,2-glycoprotein I (,2GPI). Although important in the prediction of vessel occlusion, hyperlipidemia, hypertension, CRP levels, and diabetes were less accurate. Conclusion: The results of the current study, if reproduced in a larger population, may establish an integrated system based on the creation of artificial neural networks by which to predict the extent of atherosclerosis in a given subject fairly and noninvasively. [source] | |||||||||||||