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Inflammatory Disorders (inflammatory + disorders)
Kinds of Inflammatory Disorders Selected AbstractsPhotodynamic Therapy for the Treatment of Cutaneous Neoplasia, Inflammatory Disorders, and PhotoagingDERMATOLOGIC SURGERY, Issue 5 2009EMILY TIERNEY MD BACKGROUND Photodynamic therapy (PDT) has demonstrated high efficacy, minimal side effects, and improved cosmetic outcome when used for the treatment of actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma, and photoaging. METHODS To review the literature on the use of PDT in dermatologic surgery using MEDLINE. RESULTS Published clinical studies using PDT in the treatment of AKs yield overall efficacy rates ranging from 50% to 71% with one treatment to as high as 88% to 90% with two or more treatments. For superficial BCC, initial clearance rates were 76% to 97%, and for Bowen's disease, initial clearance rates ranged from 72% to 94% overall. The use of PDT for photorejuvenation is a relatively new application of this technology, which has shown promise in improving the appearance of fine lines, pigmentary variation, and telangiectasias. CONCLUSIONS The advantages of photodynamic therapy include the capacity for noninvasive targeted therapy through topical application of aminolevulinic acid and methyl aminolevulinic acid, with outstanding cosmetic results. Although the theory behind the use of chemical photosensitizers and ultraviolet light to treat a wide variety of skin disorders is straightforward, the practical application of this technology is evolving. Additional research into the precise mechanisms of action for specific photosensitizers and optimal light sources will be highly beneficial to the advancement of this technology. [source] Adalimumab for treatment of moderate to severe psoriasis and psoriatic arthritisDERMATOLOGIC THERAPY, Issue 2008M. R. Bongiorno ABSTRACT: Psoriasis and psoriatic arthritis are common diseases associated with considerable morbidity and disability. Their pathophysiology comprises similar processes leading to inflammation of skin, entheses, and joints. Although traditional systemic agents can be effective, their use may be limited by lack of efficacy and concerns regarding adverse effects. The objective of this study was to assess the efficacy and safety of adalimumab, a fully human antitumor necrosis factor (anti-TNF) monoclonal antibody, over 16 weeks. The present authors report their personal experience in 15 patients with severe plaque psoriasis and psoriatic arthritis, refractory to other treatments, in which a decisive regression of joint/skin involvement was obtained. Psoriasis and psoriatic arthritis are chronic inflammatory disorders resulting from a combination of genetic and environmental factors. [source] Design and engineering human forms of monoclonal antibodiesDRUG DEVELOPMENT RESEARCH, Issue 3 2004Manuel L. Penichet Abstract The antibody molecule has multiple properties that make it a key component of the immune response. These include its ability to recognize a vast array of different foreign substrates and to interact with and activate the host effector systems. Antibodies with defined specificities may serve as "magic bullets" for the diagnosis and therapy of multiple diseases. With the development of the hybridoma technology, it was possible to produce rodent (mouse or rat) monoclonal antibodies that are the product of a single clone of antibody producing cells and have only one antigen binding specificity. However, the therapeutic use of rodent monoclonals antibodies in humans is limited by their immunogenicity, short circulating half-life, and inability to efficiently trigger human effector mechanisms. However, it proved difficult to produce human monoclonal antibodies using the same methods. To address these problems genetic engineering and expression systems have instead been used to produce chimeric, humanized, and totally human antibodies as well as antibodies with novel structures and functional properties. In addition, the use of yeast and human artificial chromosome vectors for animal transgenesis has allowed the development of animal models that produce antigen specific antibodies that are totally human. As a consequence, recombinant antibody-based therapies are now used to treat a variety of clinical conditions including infectious diseases, inflammatory disorders, and cancer. This article summarizes and compares different strategies for designing and engineering human antibodies and their derivatives. Drug Dev. Res. 61:121,136, 2004. © 2004 Wiley-Liss, Inc. [source] Active immunization with IL-1 displayed on virus-like particles protects from autoimmune arthritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2008Gunther Spohn Abstract IL-1 is an important mediator of inflammation and a major cause of tissue damage in rheumatoid arthritis (RA). Therapeutic administration of recombinant IL-1 receptor antagonist (IL-1Ra) is efficacious in reducing clinical symptoms of disease, but suffers from several drawbacks, including the need for frequent administrations of large amounts. Here, we show that immunization of mice with either IL-1, or IL-1, chemically cross-linked to virus-like particles (VLP) of the bacteriophage Q, elicited a rapid and long-lasting autoantibody response. The induced Ab efficiently neutralized the binding of the respective IL-1 molecules to their receptors in vitro and their pro-inflammatory activities in vivo. In the collagen-induced arthritis model, both vaccines strongly protected mice from inflammation and degradation of bone and cartilage. Moreover, immunization with either vaccine showed superior efficacy than daily administrations of high amounts of IL-1Ra. In the T and B cell-independent collagen Ab transfer model, immunization with the IL-1, vaccine strongly protected from arthritis, whereas immunization with the IL-1, vaccine had no effect. Our results suggest that active immunization with IL-1,, and especially IL-1, conjugated to Q, VLP, might become an efficacious and cost-effective new treatment option for RA and other systemic IL-1-dependent inflammatory disorders. [source] Regulation of inflammation by PPARs: a future approach to treat lung inflammatory diseases?FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2006Julien Becker Abstract Lung inflammatory diseases, such as acute lung injury (ALI), asthma, chronic obstructive pulmonary disease (COPD) and lung fibrosis, represent a major health problem worldwide. Although glucocorticoids are the most potent anti-inflammatory drug in asthma, they exhibit major side effects and have poor activity in lung inflammatory disorders such as ALI or COPD. Therefore, there is growing need for the development of alternative or new therapies to treat inflammation in the lung. Peroxisome proliferator-activated receptors (PPARs), including the three isotypes PPAR,, PPAR, (or PPAR,) and PPAR,, are transcription factors belonging to the nuclear hormone receptor superfamily. PPARs, and in particular PPAR, and PPAR,, are well known for their critical role in the regulation of energy homeostasis by controlling expression of a variety of genes involved in lipid and carbohydrate metabolism. Synthetic ligands of the two receptor isotypes, the fibrates and the thiazolidinediones, are clinically used to treat dyslipidaemia and type 2 diabetes, respectively. Recently however, PPAR, and PPAR, have been shown to exert a potent anti-inflammatory activity, mainly through their ability to downregulate pro-inflammatory gene expression and inflammatory cell functions. The present article reviews the current knowledge of the role of PPAR, and PPAR, in controlling inflammation, and presents different findings suggesting that PPAR, and PPAR, activators may be helpful in the treatment of lung inflammatory diseases. [source] Abstract no.: 10 DNA fragmentation, but not caspase-3 activation or PARP-1 cleavage, combined with macrophage immunostaining as a tool to study phagocytosis of apoptotic cells in situFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2006Dorien M. Schrijvers Efficient phagocytosis of cells undergoing apoptosis by macrophages is important to prevent immunological responses and development of chronic inflammatory disorders, such as systemic lupus erythematosus, cystic fibrosis or atherosclerosis. To study phagocytosis of apoptotic cells (AC) by macrophages in tissue, we validated different apoptosis markers (DNA fragmentation, caspase-3 activation and cleavage of its substrate poly (ADP-ribose) polymerase-1) in combination with macrophage immunostaining. Human tonsils were used as a model because they show a high apoptosis frequency under physiological conditions as well as efficient phagocytosis of AC by macrophages. On the other hand, advanced human atherosclerotic plaques were examined since phagocytosis of AC in a plaque is severely impaired. Our results demonstrate that the presence of non-phagocytized TUNEL-positive AC represents a suitable marker for poor phagocytosis by macrophages in situ. Other markers for apoptosis, such as cleavage of caspase-3 or PARP-1, should not be used to assess phagocytosis efficiency, because activation of the caspase cascade and cleavage of their substrates can occur in AC when they have not yet been phagocytized by macrophages. [source] Adenosine receptors: promising targets for the development of novel therapeutics and diagnostics for asthmaFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2006Cristina Russo Abstract Interest in the role of adenosine in asthma has escalated considerably since the early observation of its powerful bronchoconstrictor effects in asthmatic but not normal airways. A growing body of evidence has emerged in support of a proinflammatory and immunomodulatory role for the purine nucleoside adenosine in the pathogenic mechanisms of chronic inflammatory disorders of the airways such as asthma. The fact that adenosine enhances mast cell allergen-dependent activation, that elevated levels of adenosine are present in chronically inflamed airways, and that adenosine given by inhalation cause dose-dependent bronchoconstriction in subjects with asthma emphasizes the importance of adenosine in the initiation, persistence and progression of these common inflammatory disorders of the airways. These distinctive features of adenosine have been recently exploited in the clinical and research setting to identify innovative diagnostic applications for asthma. In addition, because adenosine exerts its multiple biological activities by interacting with four adenosine receptor subtypes, selective activation or blockade of these receptors may lead to the development of novel therapies for asthma. [source] Secretion of matrix metalloproteinase-9 by the proinflammatory cytokine, IL-1,: a role for the dual signalling pathways, Akt and ErkGENES TO CELLS, Issue 6 2003A. R. M. Ruhul Amin Background: Matrix metalloproteinases including MMP-9 mediate matrix destruction during chronic inflammatory diseases such as arthritis and atherosclerosis. MMP-9 up-regulation by inflammatory cytokines involve interactions between several transcription factors including activator protein-1 and NF,B. The upstream regulatory pathways are less well understood. Results: To search for the mechanism of tissue destruction in the process of inflammatory disorders, we investigated the signalling pathway critical for the activation of MMP-9 expression and secretion by IL-1,. Treatment of Balb 3T3 cells with IL-1, activated MMP-9 transcription and subsequent secretion in a time- and dose-dependent manner. Concomitantly, IL-1, treatment of cells activated phosphorylation of Akt, Erk and p38. Treatment of cells with either LY294002, a PI3K inhibitor, or expression of a dominant negative form of Akt drastically suppressed the IL-1,-dependent secretion of MMP-9. Pretreatment of cells with a MEK1 inhibitor, U0126, also strongly inhibited IL-1,-dependent secretion of MMP-9. In contrast, pre-treatment with a specific p38 kinase inhibitor, SB203580, had no effect on IL-1,-dependent secretion of MMP-9. In addition, cells expressing constitutively active form of Akt or MEK1 showed no clear activation of MMP-9 secretion, whereas these cells responded well to IL-1, treatment. However, co-transfection of cells with both active Akt and MEK1 was sufficient to induce MMP-9 secretion without stimulation with IL-1,. Conclusion: Taken together, our results suggest that IL-1, stimulation of cells activates MMP-9 secretion by the activation of the dual signalling pathways, the PI3K-Akt and MEK1-Erk and constitutive activation of these pathways were sufficient to induce MMP-9 secretion. [source] Toll-like receptors, endogenous ligands, and systemic autoimmune diseaseIMMUNOLOGICAL REVIEWS, Issue 1 2005Ian R. Rifkin Summary:, The critical role of Toll-like receptors (TLRs) as mediators of pathogen recognition by the innate immune system is now firmly established. Such recognition results in the initiation of an inflammatory immune response and subsequent instruction of the adaptive immune system, both of which are designed to rid the host of the invading pathogen. More controversial is the potential role of TLRs in the recognition of endogenous ligands and what effect this might have on the consequent development of autoimmune or other chronic sterile inflammatory disorders. An increasing number of studies implicate TLRs as being involved in the immune response to self-molecules that have in some way been altered from their native state or accumulate in non-physiologic sites or amounts, although questions have been raised about possible contaminants in certain of these studies. In this review, we discuss the evidence for endogenous ligand,TLR interactions with particular emphasis on mammalian chromatin, systemic lupus erythematosus, and atherosclerosis. Overall, the data support the general concept of a role for TLRs in the recognition of endogenous ligands. However, the precise details of the interactions and the extent to which they may contribute to the pathogenesis of human disease remain to be clarified. [source] Augmentation of endogenous cannabinoid tone modulates lipopolysaccharide-induced alterations in circulating cytokine levels in ratsIMMUNOLOGY, Issue 2 2008Michelle Roche Summary The endogenous cannabinoid system plays an important role in regulating the immune system. Modulation of endogenous cannabinoids represents an attractive alternative for the treatment of inflammatory disorders. This study investigated the effects of URB597, a selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme catalysing degradation of the endogenous cannabinoid anandamide, and AM404, an inhibitor of anandamide transport, on lipopolysaccharide (LPS)-induced increases in plasma cytokine levels in rats. Both URB597 and AM404 potentiated the LPS-induced increase in plasma tumour necrosis factor-, (TNF-,) levels. The peroxisome proliferator-activated receptor , (PPAR,) antagonist, GW9662, attenuated the AM404-induced augmentation of TNF-, levels. Furthermore, the selective cannabinoid CB1 and CB2 receptor antagonists, AM251 and AM630 respectively, and the transient receptor potential vanilloid receptor-1 (TRPV1) antagonist, SB366791, reduced LPS-induced TNF-, plasma levels both alone and in combination with AM404. In contrast, AM404 inhibited LPS-induced increases in circulating interleukin-1, (IL-1,) and IL-6. AM251 attenuated the immunosuppressive effect of AM404 on IL-1,. None of the antagonists altered the effect of AM404 on LPS-induced IL-6. Moreover, AM251, AM630 and SB366791, administered alone, inhibited LPS-induced increases in plasma IL-1, and IL-6 levels. In conclusion, inhibition of endocannabinoid degradation or transport in vivo potentiates LPS-induced increases in circulating TNF-, levels, an effect which may be mediated by PPAR, and is also reduced by pharmacological blockade of CB1, CB2 and TRPV1. The immunosuppressive effect of AM404 on IL-1, levels is mediated by the cannabinoid CB1 receptor. Improved understanding of endocannabinoid-mediated regulation of immune function has fundamental physiological and potential therapeutic significance. [source] Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthmaIMMUNOLOGY, Issue 2 2006Marian L. Kruzel Summary Pollen grains contain reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidases and in contact with mucosal surfaces generate superoxide anion (O2,,). In the presence of iron, O2,, may be converted to more reactive oxygen radicals, such as to H2O2 and/or ,OH, which may augment antigen-induced airway inflammation. The aim of the study was to examine the impact of lactoferrin (LF), an iron-binding protein, on ragweed (Ambrosia artemisiifolia) pollen extract (RWE)-induced cellular oxidative stress levels in cultured bronchial epithelial cells and accumulation of inflammatory and mucin-producing cells in airways in a mouse model of allergic airway inflammation. Results show that LF lowered RWE-induced increase in cellular reactive oxygen species (ROS) levels in bronchial epithelial cells. Most importantly, LF significantly decreased accumulation of eosinophils into airways and subepithelium of intranasally challenged, sensitized mice. LF also prevented development of mucin-producing cells. Amb a 1, the major allergenic ragweed pollen antigen lacking NAD(P)H oxidase activity, induced low-grade airway inflammation. When administered along with glucose oxidase (G-ox), a superoxide-generating enzyme, Amb a 1 induced robust airway inflammation, which was significantly lowered by LF. Surprisingly, LF decreased also inflammation caused by Amb a 1 alone. Iron-saturated hololactoferrin had only a marginal effect on RWE-induced cellular ROS levels and RWE- or Amb a 1 plus G-ox-induced inflammation. We postulate that free iron in the airways chemically reduces O2,, to more reactive species which augment antigen-induced inflammation in a mouse model of asthma. Our results suggest the utility of LF in human allergic inflammatory disorders. [source] Efficacy of methotrexate in ulcerative colitis: Failure or promiseINFLAMMATORY BOWEL DISEASES, Issue 8 2010Hans H. Herfarth MD Abstract Background: Low-dose methotrexate is a widely used and efficacious therapy in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. Prospective randomized controlled trials have demonstrated the efficacy of parenteral methotrexate in Crohn's disease (CD). We performed a systematic review of the efficacy of methotrexate in ulcerative colitis (UC) and discuss the results in the context of the known pharmacokinetics and adverse events of methotrexate therapy in inflammatory bowel diseases and other inflammatory conditions. Materials and Methods: We performed a systematic review of the literature in Medline, Embase, and Web of Science. All publications describing patients with UC treated with methotrexate were included. Results: We identified 12 studies or retrospective case series and 5 meeting abstracts that met the inclusion criteria. Only 1 study reported a prospective randomized placebo-controlled trial using methotrexate at a dose of 12.5 mg orally with no significant clinical benefit. However, the majority of uncontrolled retrospective analyses suggest a clinical response to methotrexate therapy in a range of 30%,80% when the drug is applied by parenteral route in doses between 20,25 mg. Conclusions: The only randomized controlled trial of methotrexate in UC employed oral dosing and doses lower than those shown to be effective in CD and did not demonstrate efficacy, whereas uncontrolled, retrospective studies using doses and routes of administration similar to those employed in CD suggest benefit. Well-designed, prospective, placebo-controlled trials of methotrexate in UC are needed. Inflamm Bowel Dis 2010 [source] Runt-related transcription factor 3 is associated with ulcerative colitis and shows epistasis with solute carrier family 22, members 4 and 5INFLAMMATORY BOWEL DISEASES, Issue 12 2008Rinse K. Weersma MD Abstract Background: Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are intestinal inflammatory disorders with a complex genetic background. Mice deficient for the runt-domain-transcription-factor3 (Runx3) develop spontaneous colitis. Human RUNX3 resides in an IBD-susceptibility locus. We studied the association of RUNX3 in a cohort of IBD patients and analyzed the interaction with SLC22A4/5. RUNX3 and OCTN1 mRNA expression was assessed in inflamed and noninflamed mucosa from patients and controls. Methods: 543 IBD patients (309 CD / 234 UC) and 296 controls were included. Four single nucleotide polymorphisms (SNPs) and 4 microsatellite markers were studied for RUNX3. Five SNPs (including SNP-207G,C and SNP1672C,T) were analyzed for SLC22A4/5. RUNX3, and OCTN1 expression in mucosal tissue from 30 patients (14 UC / 16 CD) and 6 controls were determined by quantitative polymerase chain reaction. Results: A significant association between RUNX3 -SNP rs2236851 and UC (OR 1.61; 95% confidence interval [CI] 1.11,2.32, P = 0.020) was found. Carriership is associated with pancolitis (odds ratio [OR] 1.86; 95% CI 1.08,3.21). SLC22A4/5 -SNPs rs272893 and rs273900 are associated with CD (OR 2.16; 95% CI 1.21,3.59 and OR 2.40; 95% CI 1.43,4.05). We found epistasis for carriership of a risk-associated allele in RUNX3 and SLC22A4/5 for UC patients versus CD patients (OR 3.83; 95% CI 1.26,11.67). RUNX3 mRNA expression is increased (P = 0.01) in inflamed colonic mucosa of UC patients compared to noninflamed mucosa and controls. Conclusions: We provide evidence for the genetic association of RUNX3 with UC and for CD with the IBD5 locus including SLC22A4/5. An epistatic effect of RUNX3 and SLC22A4 was associated with an increased risk for UC. Our data suggest a role for RUNX3 in UC susceptibility. (Inflamm Bowel Dis 2008) [source] Tetomilast suppressed production of proinflammatory cytokines from human monocytes and ameliorated chronic colitis in IL-10-deficient miceINFLAMMATORY BOWEL DISEASES, Issue 11 2008Hitoshi Ichikawa MD Abstract Background: Tetomilast (OPC-6535) was originally developed as a compound inhibiting superoxide production in neutrophils. Although its mechanism of action is not completely understood, phosphodiesterase type 4 inhibitory function has been postulated. The therapeutic effect of PDE4 inhibitors has been reported for chronic inflammatory disorders such as chronic obstructive pulmonary diseases. In this study we aimed to examine whether tetomilast could be a novel drug for inflammatory bowel diseases by further clarifying its antiinflammatory effects. Methods: Cytokines from human peripheral blood mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and Cytokine Beads Array. The transcripts were quantified by reverse-transcriptase polymerase chain reaction (RT-PCR). Phosphorylation of transcription factors was examined by phosflow. To examine its in vivo effect, a once-daily oral dose of tetomilast was tested in murine IL-10,/, chronic colitis. Results: Tetomilast suppressed TNF-, and IL-12 but not IL-10 production from lipopolysaccharide (LPS)-stimulated human monocytes. It suppressed TNF-,, IFN-,, and IL-10 from CD4 lymphocytes. Tetomilast suppressed cytokine production at the transcriptional level but did not alter phosphorylation of p65, ERK, p38, and STAT3. HT-89, a protein kinase A inhibitor, did not abolish the effect of tetomilast, suggesting that it was independent from the classical cAMP/PKA pathway. IL-10 was not essential to the inhibitory effect of tetomilast on TNF-, and IL-12. Tetomilast ameliorated IL-10,/, chronic colitis with reduced clinical symptoms, serum amyloid A, and histological scores with decreased TNF-, mRNA expression. Conclusions: Tetomilast exerts its antiinflammatory effects on human monocytes and CD4 cells. Combined with in vivo data these findings support the feasibility of tetomilast as a novel drug for inflammatory bowel diseases. (Inflamm Bowel Dis 2008) [source] Un-promoted issues in inflammatory bowel disease: opportunities to optimize careINTERNAL MEDICINE JOURNAL, Issue 3 2010J. M. Andrews Abstract Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the gut, which lead to significant morbidity and impaired quality of life (QoL) in sufferers, without generally affecting mortality. Despite CD and UC being chronic, life-long illnesses, most medical management is directed at acute flares of disease. Moreover, with more intensive medical therapy and the development of biological therapy, there is a risk that management will become even more narrowly focused on acute care, and be directed only at those with more severe disease, rather than encompassing all sufferers and addressing important non-acute issues. This imbalance of concentration of medical attention on ,high-end' care is in part driven by the need to perform and publish randomized clinical trials of newer therapies to obtain registration and licensing for these agents, which thus occupy a large proportion of the recent IBD treatment literature. This leads to less attention on relatively ,low-technology' issues including: (i) the psychosocial burden of chronic disease, QoL and specific psychological comorbidities; (ii) comorbidity with functional gastrointestinal disorders (FGIDs); (iii) maintenance therapy, monitoring and compliance; (iv) smoking (with regard to CD); (v) sexuality, fertility, family planning and pregnancy; and (vi) iron deficiency and anaemia. We propose these to be the ,Un-promoted Issues' in IBD and review the importance and treatment of each of these in the current management of IBD. [source] Chronic necrotizing pulmonary aspergillosis in a patient treated with a tumor necrosis factor-, inhibitorINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2010Eun Jung LEE Abstract Tumor necrosis factor (TNF)-, is a pro-inflammatory cytokine that plays an important role in the pathogenesis of a variety of autoimmune diseases. TNF-, inhibitors have been shown to offer clinical benefits in the treatment of autoimmune and inflammatory disorders, including rheumatoid arthritis, ankylosing spondylitis (AS), and Crohn's disease. Occasionally, these agents have been associated with infectious complications because of their immunosuppressive activity. Globally, several cases of infections associated with TNF-, inhibitors have been reported. However, Aspergillus infection associated with etanercept is very rare. We report a case of chronic necrotizing pulmonary aspergillosis in a 51-year-old man with AS that developed after treatment with etanercept. [source] Changes in adipocytes and dendritic cells in lymph node containing adipose depots during and after many weeks of mild inflammationJOURNAL OF ANATOMY, Issue 6 2005Dawn Sadler Abstract The time course and cellular basis for inflammation-induced hypertrophy of adipose tissue were investigated over 20 weeks in mature male rats. Mild inflammation was induced by subcutaneous injection of 20 µg lipopolysaccharide into one hind-leg three times/week for 4 or 8 weeks, followed by up to 12 weeks ,rest' without intervention. Mean volume and frequency of apoptosis (TUNEL assay) were measured in adipocytes isolated from sites defined by their anatomical relations to lymph nodes, plus numbers of CCL21-stimulated lymph node-derived and adipose tissue-derived dendritic cells. Experimental inflammation increased dendritic cells and adipocyte apoptosis in the locally stimulated popliteal depot and the lymphoid tissue-associated regions of the contralateral popliteal and mesentery and omentum. Responses declined slowly after inflammation ended, but all measurements from the locally stimulated popliteal depot, and the omentum, were still significantly different from controls after 12 weeks rest. The locally stimulated popliteal adipose tissue enlarged by 5% within 4 weeks and remained larger than the control. We conclude that prolonged inflammation induces permanent enlargement, greater adipocyte turnover and increased dendritic cell surveillance in the adjacent adipose tissue and the omentum. The experiment suggests a mechanism for selective hypertrophy of lymphoid tissue-associated adipose tissue in chronic stress and inflammatory disorders, including impaired lymph drainage, Crohn's disease and HIV-associated lipodystrophy, and a link between evolutionary fitness, sexual selection and aesthetically pleasing body symmetry. It would be useful for further study of molecular mechanisms in inflammation-induced local hypertrophy of adipose tissue and development of specific therapies that avoid interference with whole-body lipid metabolism. [source] Localized lymphedema (elephantiasis): a case series and review of the literatureJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2009Song Lu Background:, Lymphedema typically affects a whole limb. Rarely, lymphedema can present as a circumscribed plaque or an isolated skin tumor. Objective:, To describe the clinical and pathologic characteristics and etiologic factors of localized lymphedema. Methods:, Case,control study of skin biopsy and excision specimens histologically diagnosed with lymphedema and presenting as a localized skin tumor identified during a 4-year period. Results:, We identified 24 cases of localized lymphedema presenting as solitary large polyps (11), solid or papillomatous plaques (7), pendulous swellings (4), or tumors mimicking sarcoma (2). Patients were 18 females and 6 males with a mean age of 41 years (range 16,74). Anogenital involvement was most frequent (75%) , mostly vulva (58%), followed by eyelid (13%), thigh (8%) and breast (4%). Causative factors included injury due to trauma, surgery or childbirth (54%), chronic inflammatory disease (rosacea, Crohn's disease) (8%), and bacterial cellulitis (12%). Eighty-five percent of these patients were either overweight (50%) or obese (35%). Compared with a series of 80 patients with diffuse lymphedema, localized lymphedema patients were significantly younger (41 vs. 62 years old, p = 0.0001), had no history of cancer treatment (0% vs. 18%, p = 0.03), and had an injury to the affected site (54% vs. 6%, p = 0.0001). Histologically, all cases exhibited dermal edema, fibroplasia, dilated lymphatic vessels, uniformly distributed stromal cells and varying degrees of papillated epidermal hyperplasia, inflammatory infiltrates and hyperkeratosis. Tumor size significantly and positively correlated with history of cellulitis, obesity, dense inflammatory infiltrates containing abundant plasma cells, and lymphoid follicles (p < 0.05). A history of cellulitis, morbid obesity, lymphoid follicles and follicular cysts predicted recurrent or progressive swelling despite excision (p < 0.05). Conclusions:, Localized lymphedema should be considered in the etiology of skin tumors when assessing a polyp, plaque, swelling or mass showing dermal edema, fibrosis and dilated lymphatics on biopsy. A combination of lymph stasis promoting factors (trauma, obesity, infection and/or inflammatory disorders) produces localized elephantiasis. [source] Inflammatory dermatoses of the vulvaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2005Lauren A. Hammock A wide range of inflammatory disorders may occur on the vulva, and they may have a similar clinical presentation to HPV lesions. However, HPV is incurable and often is treated surgically. Accordingly, as inflammatory dermatoses commonly occur on the vulva and are often curable with topical therapy, an awareness of these entities and an ability to distinguish them from HPV are imperative. [source] Subtle intracorneal findings in inflammatory disorders: hyphae or not?JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2004Sarolta K. Szabo Background:, Spongiotic and lichenoid dermatitides are frequently stained with periodic acid-Schiff (PAS) stains to check for the presence of dermatophytes. PAS+ structures without a septate morphology are often seen with lichenoid dermatitides, however, their nature has not been previously characterized. Methods:, Fifteen consecutive biopsies of lichenoid and five spongiotic dermatitides were stained with hematoxylin and eosin (H&E), PAS, and antibodies to CD1a. Results:, Twelve of 15 lichenoid and none of the five spongiotic dermatitis showed PAS+ structures in the stratum corneum. Distinct septation or branching was not identified in these PAS+ structures. Eleven of 15 from the lichenoid group, but none from the spongiotic group, showed CD1a+ structures in the stratum corneum. This staining pattern suggests that the intracorneal structures represent the dendritic processes of Langerhans' cells (LCs) within the stratum corneum. Conclusions:, PAS+ and CD1a+ structures are present in the stratum corneum of lichenoid, but not in spongiotic, dermatitis. This study morphologically confirms extension of LC dendrites into the stratum corneum in lichenoid but not in spongiotic dermatitides. [source] BIOACTIVE POLAR LIPIDS IN OLIVE OIL, POMACE AND WASTE BYPRODUCTSJOURNAL OF FOOD BIOCHEMISTRY, Issue 4 2008HARALABOS C. KARANTONIS ABSTRACT Olive oil protects against atherosclerosis because of biologically active microconstituents. In this study, total polar lipids from olive oil, pomace, pomace oil and waste byproducts were extracted, fractionated by thin layer chromatography and tested for their bioactivity. The most active ones were further purified on high-performance liquid chromatography, and the resulting lipid fractions were tested for their bioactivity. Bioactive compounds were determined in all samples with the exception of olive pomace oil. These lipids inhibited platelet-activating factor (PAF)-induced platelet aggregation and also induced platelet aggregation. The bioactive compound from olive pomace has been chemically characterized as a glycerylether-sn-2-acetyl glycolipid based on mass spectra. Chemical determinations and mass spectrometry data reinforce the assumption that these active microconstituents share both similar bioactivity and common structural features. The existence of PAF antagonists in polar lipid extracts from olive oil waste by-products render them biologically valuable materials for the food industry that could be used for the production of functional foods. PRACTICAL APPLICATIONS Isolated bioactive polar lipids from waste by-products of the olive oil industry that act as inhibitors of platelet-activating factor (PAF) may be used for enrichment and production of foods with higher nutritional value, as PAF plays a major role in inflammatory disorders, including atherosclerosis development. [source] Autoimmune and inflammatory disorders and risk of malignant lymphomas , an updateJOURNAL OF INTERNAL MEDICINE, Issue 6 2008K. E. Smedby Abstract. As specific autoimmune disorders now constitute established risk factors for malignant lymphomas, we describe this association. We review reported risk levels, risk determinants, lymphoma subtypes and biological mechanisms in autoimmunity/inflammation, emphasizing on recent findings. Whilst numerous reports describe average lymphoma risks in large patient groups, there's a recent shift of focus to risk determinants and the role of inflammatory activity. Studies highlight associations with diffuse large B-cell lymphoma, apart from lymphoma development in target organs of inflammation. Future studies of high-risk patient subsets using detailed assessments of autoimmunity/inflammation and lymphoma may give important clues to lymphomagenesis. [source] Clinical aspects of parvovirus B19 infectionJOURNAL OF INTERNAL MEDICINE, Issue 4 2006K. BROLIDEN Abstract. Parvovirus B19 is a significant human pathogen that causes a wide spectrum of clinical complications ranging from mild, self-limiting erythema infectiosum in immunocompetent children to lethal cytopenias in immunocompromised patients and intrauterine foetal death in primary infected pregnant women. The infection may also be persistent and can mimic or trigger autoimmune inflammatory disorders. Another important clinical aspect to consider is the risk of infection through B19-contaminated blood products. Recent advances in diagnosis and pathogenesis, new insights in the cellular immune response and newly discovered genotypes of human parvoviruses form a platform for the development of modern therapeutic and prophylactic alternatives. [source] Nitric oxide synthase type-II is synthesized by human gingival tissue and cultured human gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2000H. K. Kendall Nitric oxide is known to be an important inflammatory mediator, and is implicated in the pathophysiology of a range of inflammatory disorders. The aim of this study was to determine the localization and distribution of endothelial NOS (NOSII) in human gingival tissue, and to ascertain if human gingival fibroblasts express NOS-II when stimulated with interferon gamma (IFN-,) and bacterial lipopolysaccharide (LPS). The distribution of NOS-II in inflamed and non-inflamed specimens of human gingivae was studied using a monoclonal antibody against nitric oxide synthase II. Cultures of fibroblasts derived from healthy human gingivae were used for the cell culture experiments. The results from immunohistochemical staining of the tissues indicated an upregulation of NOS-II expression in inflamed compared to non-inflamed gingival tissue. Fibroblasts and inflammatory cells within the inflamed connective tissue were positively stained for NOS-II. In addition, basal keratinocytes also stained strongly for NOS-II, in both healthy and inflamed tissue sections. When cultured human gingival fibroblasts were stimulated by INF-, and Porphyromonas gingivalis LPS, NOS-II was more strongly expressed than when the cells were exposed to LPS or IFN-, alone. These data suggest that, as for other inflammatory diseases, NO plays a role in the pathophysiology of periodontitis. [source] Idiopathic granulomatous and necrotising inflammatory disorders of the canine central nervous system: a review and future perspectivesJOURNAL OF SMALL ANIMAL PRACTICE, Issue 3 2010Lauren R. Talarico Granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, and necrotizing leukoencephalitis are common inflammatory conditions of the canine central nervous system. Although each disease has unique histopathological features, these canine disorders collectively seem to be aberrant immune responses directed against the central nervous system. A review of the neurological signs and general neurodiagnostic approach to canine meningoencephalitis is followed by an overview of the specific clinical and neuropathological features of granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, and necrotizing leukoencephalitis. The aetiopathogenesis of each disorder is explored including potential genetic, immunological, and environmental factors along with the current and prospective immunomodulatory therapies for meningoencephalitis. [source] Complications of exploratory coeliotomy in 70 catsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 7 2004S. Lester Records of all cats that had undergone exploratory coeliotomy at the University of Edinburgh during the period November 1995 to July 2002 were reviewed. Seventy records were retrieved. There were 30 cats in which infection or inflammatory disorders predominated, 17 cats with neoplasia, three cats with trauma and 20 cats with other disorders. Exploratory coeliotomy was performed for diagnostic purposes in 28 cats (40 per cent), treatment in 34 cats (49 per cent) and for diagnosis and treatment in eight cats (11 per cent). Methods of intraoperative diagnosis included incisional biopsy of abdominal organs (52 cats), cytology (two cats), microbiology (17 cats) and gross appearance (17 cats). Fifty-eight cats (83 per cent) survived the hospitalisation period. Complications occurred in 18 cats (26 per cent) and were related to anaesthesia (four cats), the underlying disease process (15 cats), surgery (five cats) and were undetermined in one cat. [source] Enhanced B7 Costimulatory Molecule Expression In Inflammatory Human Sural Nerve BiopsiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001R Kiefer Objectives-To define the role of the costimulatory molecules B7-1 and B7-2 in inflammatory disorders of the peripheral nervous system. B7 molecules are essential for effective antigen presentation and may determine the differentiation of T cells into a Th-1 or Th-2 phenotype, thus modulating immune response and disease course. Methods-Forty nine sural nerve biopsies from patients with neuroborreliosis, Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), CIDP variants and hereditary neuropathies, and those with no detectable abnormality were investigated. The expression of B7-1 and B7-2 mRNA and protein was investigated by polymerase chain reaction (PCR) and immunocytochemistry. Results-B7-1 mRNA was strongly upregulated in both cases of neuroborreliosis, in two cases of GBS and one case of variant CIDP. Moderate to low levels were detected in the remaining GBS and CIDP biopsies and were rarely found in a noninflammatory control group consisting of hereditary neuropathy and normal nerves. At the immunocytochemical level, strong expression of B7-1 protein was found in both neuroborreliosis cases, and moderate or low expression in six of eight GBS cases and seven of 17 CIDP cases investigated, whereas only one of five non-inflammatory control nerves showed staining, which was very weak. In neuroborreliosis, B7-1 protein was found very pronounced in epineurial infiltrates, whereas in CBS and CIDP, labelling was predominantly endoneurial and localised to putative macrophages. B7-2 mRNA and protein were expressed only at low levels in neuroborreliosis and selected autoimmune neuropathy cases, and were essentially absent from noninflammatory controls. Conclusions-B7 molecules are expressed in the peripheral nervous system and regulated during disease, and their presence in macrophages underlines the putative function of endoneurial macrophages as local antigen presenting cells in the immunopathology of peripheral nerve. B7-1 rather than B7-2 is preferentially upregulated, possibly promoting the induction of a Th-1-type T cell response within the nerve. [source] Vascular and dendritic cell coagulation signaling in sepsis progressionJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009W. RUF Summary., The intrinsic signaling networks of the coagulation pathways have recently emerged as crucial determinants for survival in sepsis and systemic inflammatory response syndromes. Protease activated receptor (PAR) 1 is central to both lethality promoting and vascular protective signaling. In the vascular anticoagulant pathway, EPCR/aPC-PAR1 signaling prevents vascular leakage and genetic or acute deficiencies in this pathway promote lethality. In addition, coagulation signaling acts directly on cells of the innate immune system. Dendritic cell (DC) thrombin-PAR1 signaling is coupled to the migration promoting sphingosine 1 phosphate receptor 3 (S1P3). Thrombin generated in the lymphatic compartment perturbs DCs to promote systemic inflammation and disseminated intravascular coagulation in severe sepsis. Signaling-selective aPC variants and selective modulators of the S1P receptor system attenuate sepsis lethality, suggesting novel therapeutic approaches that can be employed to rebalance alterations in the coagulation signaling pathways in severe inflammatory disorders. [source] Angiogenesis and lymphangiogenesis in bronchial asthmaALLERGY, Issue 8 2010A. Detoraki To cite this article: Detoraki A, Granata F, Staibano S, Rossi FW, Marone G, Genovese A. Angiogenesis and lymphangiogenesis in bronchial asthma. Allergy 2010; 65: 946,958. Abstract Neovascularization plays a prominent role in inflammation and tissue remodeling in several chronic inflammatory disorders. Vessel number and size, vascular surface area and vascular leakage are all increased in biopsies from patients with asthma. High levels of VEGF and other angiogenic factors have been detected in tissues and biological samples of patients with asthma and correlate with disease activity and inversely with airway hyper-responsiveness. Inflammation in the lung stimulates the growth of new blood vessels and these contribute to the airway obstruction or airway hyper-responsiveness, or both. Effector cells of inflammation (human lung mast cells, basophils, eosinophils, macrophages, etc.) are major sources of a vast array of angiogenic and lymphangiogenic factors. Inhaled corticosteroids reduce vascularity and growth factor expression and might modulate bronchial vascular remodeling in asthma. Specific antagonists to VEGF and other angiogenic factors and their receptors might help to control chronic airway inflammation and vascular remodeling and offer a novel approach for the treatment of chronic inflammatory lung disorders. [source] Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosaALLERGY, Issue 8 2010T. Liu To cite this article: Liu T, Xie C, Chen X, Zhao F, Liu A-M, Cho D-B, Chong J, Yang P-C. Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosa. Allergy 2010; 65: 969,977. Abstract Background:, The prevalence of airway inflammatory disorders keeps rising; its pathogenic mechanism is still not fully understood. Objective:, The present study aimed to investigate the role of muscarinic receptor (M receptor) in regulating the immune cell activity in nasal mucosa by using surgical removed nasal mucosa from patients with nasal polyposis (NP) as a study platform. Methods:, Human nasal mucosal sample was collected from inferior turbinectomy of 86 patients with NP or/and allergic rhinitis. Expression of tumor necrosis factor alpha (TNF-alpha), M receptor, OX40 ligand was measured in nasal mucosa by enzyme-linked immunosorbent assay, flow cytometry, and Western blotting assay. Results:, When compared with non-NP (nNP) nasal mucosa, contents of TNF-alpha and TNF-alpha(+) cells markedly increased in NP nasal mucosa; immune staining colocalized M3 receptor(+) and TNF-alpha(+) cells in NP nasal mucosa; exposure of isolated CD4(+) T cells to methacholine induced the release of TNF-alpha. We also found CD11c(+)/M3 receptor(+) cells in NP nasal mucosa. Methacholine increased the expression of OX40L in dendritic cells. Staphylococcal (S) aureus and S. enterotoxin B (SEB) were detected in NP nasal mucosa. Exposure of dendritic cells or naïve CD4(+) T cells to SEB initiated the expression of M3 receptor at mRNA and protein levels. Conclusions:, The present data demonstrate that parasympathetic activity has the capacity to activate dendritic cells to release OX40 ligand, the latter induces CD4(+) T cells to produce IL-4 and TNF-alpha that may further contribute to the pathogenesis of NP. [source] | |||||||||||||||||||||||||||||||||||||||||||