|
| ||
|
|
||
Chronic Inflammatory Disorders (chronic + inflammatory_disorders)
Selected AbstractsAdalimumab 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] 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] 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] 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] 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] The gut, immunoregulation and micro-organisms from man's evolutionary pastNUTRITION BULLETIN, Issue 2 2010G. A. W. Rook Summary Man has moved rapidly from the hunter-gatherer environment to the living conditions of the rich industrialised countries. The hygiene hypothesis suggests that the resulting changed and reduced pattern of exposure to certain critical micro-organisms, mostly derived from mud, animals and faeces, has led to disordered regulation of the immune system and, hence, to increases in chronic inflammatory disorders such as allergies, inflammatory bowel diseases and autoimmunity. Epidemiology, backed up by laboratory models, indicates that the relevant organisms are those that have very long associations with the mammalian immune system, traceable back to the Palaeolithic or earlier. Often, these organisms have been present as commensals (notably in the intestinal microbiota), environmental ,pseudocommensals', sub-clinical infections or asymptomatic carrier states, and the mammalian immune system is in a state of ,evolved dependence' on their continued presence. Several of these ,Old Friends', often operating primarily in the gut, act as modulators of dendritic cells and T cells, leading to the establishment of immunoregulatory circuits. Clinical trials are in progress to test living helminths (Trichuris suis and Necator americanus) in allergies, inflammatory bowel disease and multiple sclerosis. We can anticipate rapid increases in the use of these and other organisms or their components in novel types of therapy with applications in several branches of medicine. Probiotics tested in clinical trials targeting chronic inflammatory disorders have so far given unconvincing results, but if strains for these indications are selected on the basis of their ability to induce immunoregulation, and not merely imposed by companies that have intellectual property rights, we can anticipate rapid progress. [source] Clinical diagnosis and differential diagnosis of CJD and vCJD,APMIS, Issue 1 2002Inga Zerr The most widely distributed form of transmissible spongiform encephalopathy, sporadic Creutzfeldt-Jakob disease, typically affects patients in their sixties. Rapidly progressive dementia is usually followed by focal neurological signs and typically myoclonus. The disease duration in sporadic CJD is shorter than in variant CJD (6 months and 14 months, respectively). The clinical diagnosis in sporadic CJD is supported by the detection of periodic sharp and slow wave complexes in the electroencephalogram, hyperintense signals in basal ganglia on magnetic resonance imaging and elevated levels of neuronal proteins in the cerebrospinal fluid (such as 14-3-3). In contrast to the sporadic form, hyperintense signals in the posterior thalamus ("pulvinar sign") are seen in variant CJD. Following recent developments in diagnostic premortem techniques, clinical criteria for probable sporadic and probable variant CJD were established. Clinicopathological studies on sporadic CJD revealed different phenotypes which are characterized by neuropathological lesion profile, clinical syndrome, codon 129 genotype and type of proteinase K-resistant core of the prion protein. Alzheimer's disease and Lewy body dementia are the most frequent differential diagnoses in sporadic CJD in elderly patients, whereas chronic inflammatory disorders of the central nervous system have to be considered in younger patients. [source] GR Ligands: Can We Improve the Established Drugs?CHEMMEDCHEM, Issue 8 2006Hartmut Rehwinkel Dr. Glucocorticoids (GCs) represent the most effective therapy for acute and chronic inflammatory disorders, yet they can elicit severe side effects. New classes of GC receptor ligands appear to have all of the benefits and fewer side effects and have prompted new research into an old drug target. Compound,A (shown) is the latest addition to this exciting development. [source] MicroRNAs: novel regulators in skin inflammationCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2008E. Sonkoly Summary Compelling evidence indicates that microRNAs (miRNAs), short, non-protein coding RNAs, are critical for the development and survival of multicellular organisms. Recently, miRNAs were implicated in the pathogenesis of psoriasis and atopic eczema (AE), the two most common chronic inflammatory disorders in skin. In particular, miR-203, the first skin-specific miRNA, showing an intriguing expression profile being confined to skin epithelium, is specifically overexpressed in psoriasis. MiR-146a, another miRNA showing specific upregulation in psoriasis, is involved in the regulation of innate immune responses and the tumour necrosis factor (TNF)-, pathway. Interestingly, miR-125b, another miRNA involved in the TNF-, pathway, is also deregulated in psoriasis and AE. As skin inflammation may serve as a model for chronic inflammatory disorders, it is likely that miRNAs involved in skin inflammation will eventually emerge in other inflammatory or autoimmune disorders, and some of these may become disease markers and therapeutic targets. In this review we present an overview of what is currently known about the roles of miRNAs in chronic inflammatory skin disorders. [source] | ||||||||||