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ID PMID Title PublicationDate abstract
15035793 Mechanisms of action of paracetamol and related analgesics. 2003 Paracetamol and salicylate are weak inhibitors of both isolated cyclooxygenase-1 (COX-1) and COX-2 but are potent inhibitors of prostaglandin (PG) synthesis in intact cells if low concentrations of arachidonic acid are available. The effects of both drugs are overcome by increased levels of hydroperoxides. At low concentrations of arachidonic acid, COX-2 is the major isoenzyme involved in PG synthesis when both COX-1 and COX-2 are present in cells. Therefore, paracetamol and salicylate may selectively inhibit PG synthesis involving COX-2 because the lower flux through this pathway produces lesser levels of the hydroperoxide, PGG(2), than the pathway involving COX-1. Apart from the lack of anti-inflammatory effect of paracetamol in rheumatoid arthritis, the clinical effects of paracetamol and salicylate are very similar and resemble those of the selective COX-2 inhibitors. A splice variant of COX-1, termed COX-3, may be a site of action of these drugs but, further work, particularly at low concentrations of arachidonic acid is required. We suggest that paracetamol, salicylate and, possibly, the pyrazolone drugs, such as dipyrone, may represent a distinct class of atypical NSAIDs which could be termed peroxide sensitive analgesic and antipyretic drugs (PSAADs).
12472502 Successful treatment of multiple bursal cysts in systemic sclerosis. 2002 Dec BACKGROUND: Bursitis frequently occurs in the various conditions of autoimmune disorders including rheumatoid arthritis, but there have been few cases of effusive bursitis in systemic sclerosis. OBJECTIVE: To present a case of systemic sclerosis with multiple bursitis on upper, lower extremities, and trunk with or without joint involvement. METHODS: Case report and review of the literature. RESULTS: Multiple asymptomatic cystic masses contained yellow and chalky sterile fluid, all of which were diagnosed as effusive bursitis. Most of them were treated with a surgical resection, a continuous drainage, and an injection of highly concentrated ethanol into their internal spaces. However, an intrabursal injection of emulsified triamcinolone acetonide was the only effective treatment for the giant mass that occurred on the right chest wall. CONCLUSION: Successful treatment of multiple bursal cysts with systemic sclerosis was presented.
12110305 Sesquiterpene lactones as inhibitors of human neutrophil elastase. 2002 Sep Human neutrophil elastase (HNE) is a serine protease that has been implicated in the abnormal turnover of connective tissue proteins and has been described as an important pathogenic factor in several inflammatory diseases such as rheumatoid arthritis or cystic fibrosis. Here we investigated 17 sesquiterpene lactones (SLs) for their ability to inhibit human neutrophil elastase in an in vitro assay. Podachaenin was the most active compound with an IC(50) value of 7 microM. SLs do not covalently bind to the amino acids of the catalytic triad, thus differing from other elastase inhibitors with a lactone moiety. In contrast to most other biological activities of SLs HNE inhibition is not mediated by alpha,beta-unsaturated carbonyl functions. Ligand binding calculations using the X-ray structure of HNE and the program FlexX revealed structural elements which are a prerequisite for their inhibitory activity.
11974490 [Epidemiology and patient management in the area of spondyloarthritis]. 2002 Feb Within the group of inflammatory rheumatic diseases, spondyloarthropathy is the most common diagnosis after rheumatoid arthritis. Its prevalence was long underestimated. Ankylosing spondylitis (AS) and undifferentiated spondyloathropathy (uSpA) are the most common subgroups in western countries. There are still difficulties in diagnosis especially of the early forms of the spondyloarthropathies. Data of socioeconomics and therapeutic options are limited. In more recent times, researchers have started to investigate the burden of disease and the socioeconomic aspects. Better diagnostic options are available and promising new therapeutic agents, especially TNF-alpha blocking agents, have been investigated. However, further studies are urgently needed for this underestimated group of diseases and are currently being performed inside the German rheumatology network.
15785438 Prevalence of HFE and TFR2 gene mutation in 118 Ligurian rheumatic patients. 2004 Dec AIM: HFE gene is associated to haemochromatosis, an inherited autosomal recessive disorder responsible of an overload of iron in intestine, liver, pancreas, heart, cutis and joints. Articular and periarticular calcifications may occur. H63D mutation may play a role in the pathogenesis of rheumatoid arthritis. METHODS: DNA of 118 consecutive patients (28 males, 90 females, mean age 58.5+/-13.44) living in Liguria and affected by different rheumatic diseases was examined to evaluate the presence of HFE mutations. RESULTS: Analysis data showed that in 45% (53/118) of patients almost one mutation of HFE gene was present and the presence of H63D mutation in the rheumatic patients was particularly elevated. Data obtained in this study have permitted to reveal that 25 patients of 53 (47.1%) with 1 of 11 HFE mutations suffered from symptomatic or silent chondrocalcinosis. CONCLUSIONS: The conclusion is drawn that this mutation may be correlated to various rheumatic diseases.
17110359 Novel approaches to the management of graves' ophthalmopathy. 2002 Apr Severe Graves' ophthalmopathy constitutes a complex therapeutic challenge and treatment outcome often is not satisfactory. Established methods of treatment include high-dose glucocorticoids, orbital radiotherapy and orbital decompression. Recently, the use of intravenous glucocorticoids has been shown to provide more favorable results than oral glucocorticoids. Novel treatments under investigation include somatostatin analogues, intravenous immunoglobulins and antioxidants. Low-dose immunosuppressive drugs (namely cyclosporine and, possibly, methotrexate) might be useful as an adjunct to established methods, particularly in view of a glucocorticoid-sparing action. Because cytokines play an important role in the pathogenesis of the disease, cytokine antagonists, which are currently evaluated in rheumatoid arthritis and other autoimmune conditions, might constitute in the future a valuable tool for the management of eye disease. Prevention of Graves' ophthalmopathy would be desirable, but so far it is limited to secondary prevention (arrest of progression of subclinical disease to clinical disease) and tertiary prevention (avoidance of deterioration or complications of clinical disease): among preventive measures smoking withdrawal is probably the most important one. Primary prevention (in the absence of disease) is only speculative, but oral tolerance induction or vaccination with the offending antigen(s) might prove beneficial for prevention of Graves' ophthalmopathy in genetically susceptible individuals.
16858479 The physiologic basis and clinical applications of cryotherapy and thermotherapy for the p 2004 Jul Cryotherapy and thermotherapy are useful adjuncts for the treatment of musculoskeletal injuries. Clinicians treating these conditions should be aware of current research findings regarding these modalities, because their choice of modality may affect the ultimate outcome of the patient being treated. Through a better understanding of these modalities, clinicians can optimize their present treatment strategies. Although cold and hot treatment modalities both decrease pain and muscle spasm, they have opposite effects on tissue metabolism, blood flow, inflammation, edema, and connective tissue extensibility. Cryotherapy decreases these effects while thermotherapy increases them. Continuous low-level cryotherapy and thermotherapy are newer concepts in therapeutic modalities. Both modalities provide significant pain relief with a low side-effect profile. Contrast therapy, which alternates between hot and cold treatment modalities, provides no additional therapeutic benefits compared with cryotherapy or thermotherapy alone. Complications of cryotherapy include nerve damage, frostbite, Raynaud's phenomenon, cold-induced urticaria, and slowed wound healing. With thermotherapy, skin burns may occur, especially in patients with diabetes mellitus, multiple sclerosis, poor circulation, and spinal cord injuries. In individuals with rheumatoid arthritis, deep-heating modalities should be used with caution because increased inflammation may occur. Whirlpool and other types of hydrotherapy have caused infections of the skin, urogenital, and pulmonary systems. Additionally, ultrasound should not be used in patients with joint prostheses.
15501187 Magnetic resonance imaging of peripheral joints in rheumatic diseases. 2004 Dec The need for better methods than the conventional clinical, biochemical and radiographical examinations in the management of inflammatory joint diseases is evident, since these methods are not sensitive or specific to early pathologies and subtle changes. Magnetic resonance imaging (MRI) offers improved sensitivity to early inflammatory and destructive changes in peripheral joints in rheumatoid arthritis (RA) and, even though less well documented, in other inflammatory joint diseases. Good evidence is available that MRI bone erosions represent true bone abnormalities and are predictors of radiographical outcome in RA. Similarly, there is solid evidence for MRI synovitis representing true synovial inflammation and being of considerable practical, clinical and radiological significance in RA. Describing the encouraging current knowledge regarding MRI for diagnosis, monitoring and prognosis, this chapter discusses the potential for the use of MRI in the clinical management of patients with suspected and diagnosed inflammatory joint diseases, as well as research priorities and clinical situations where the use of MRI could be suggested.
15251122 Tumor necrosis factor-alpha in the pathogenesis and treatment of cancer. 2004 Aug The critical pathogenic role of tumor necrosis factor (TNF)alpha in inflammatory disorders such as rheumatoid arthritis and inflammatory bowel disease is well established. The role played by TNFalpha in both the treatment and pathogenesis of cancer remains less understood. Recent advances help to create a framework for understanding seemingly paradoxical effects of TNFalpha as both an anti-tumour agent and a mediator of tumour growth. High pharmacological doses of TNFalpha combined with chemotherapy can regress otherwise intractable tumours, and efforts continue to optimize delivery to avoid severe toxicities. Mounting evidence demonstrates that pathophysiological concentrations of endogenous TNFalpha act to promote tumour genesis and growth. The cellular and molecular pathways mediating these phenomena are starting to be clarified. Current data support the continued development of both TNFalpha and anti-TNFalpha therapy for clinical treatment of cancers in distinct settings.
15202088 [Angiogenesis in human cerebral ischemia]. 2004 Jun 1 OBJECTIVE: We aimed to review current knowledge about angiogenesis processes following stroke and possible benefit of future therapeutic angiogenic-related treatments. DEVELOPMENT: Angiogenesis is a physiopathologic process where new vessels arise from pre-existing ones within different phases: sprouting and maturation. To modulate angiogenesis there is a balance between several promoters like VEGF, bFGF, MMPs, etc. but also with inhibitors or angiostatic molecules such as angiostatin, endostatin, etc. In human pathologies angiogenesis has a dual effect: useful in wound healing, tissue remodelling or ischemic heart disease but harmful in cancer, rheumatoid arthritis or atheroma plaque instability and rupture. Angiogenesis is involved in some cerebrovascular diseases. Following ischemic stroke there is an overexpression of several molecules related with this process, although its finality remains largely unknown. CONCLUSION: Angiogenesis is activated after stroke modifying capillary network. To obtain advantages from angiogenesis, it will be essential to achieve the temporal profile of these molecules in humans, and to investigate if its effects are different in acute or chronic stroke phases. In the future, angiogenesis modulation could take part of a combined stroke therapy.
15095631 [T'ai chi in the elderly: practical aspects]. 2003 Nov New approaches to health promotion for the growing geriatric population are needed. Low to moderately intense exercise programs, such as T'ai Chi seem particularly appropriate for older individuals because of many worthwhile physiological and psychological long-term benefits. T'ai Chi reduces falls and improves postural stability in older adults. It also has a positive impact on muscle strength and cardiovascular fitness and can improve mobility in patients with rheumatoid arthritis. It imparts a sense of well-being and confidence, and can reduce fear of falling in older adults. This article reviews the current medical literature regarding the multiple effects of T'ai Chi. Historical aspects of T'ai Chi and its current adaptation for practice by healthy older adults are presented. Finally, a set of modified exercises is proposed that is based on underlying principles of T'ai Chi and can be applied to patients with mild to moderate cognitive impairment.
15074721 Rupture of the extensor pollicis longus tendon: a study of aetiological factors. 2004 Although rupture of the extensor pollicis longus (EPL) tendon is a well-known complication of distal radial fractures, a number of patients rupture the EPL because of other conditions. We have retrospectively studied the aetiology of 27 ruptures of the EPL in 26 consecutive patients. Of 19 patients with injured wrists 12 had distal radial fractures, five had blunt trauma, and two had stab wounds that resulted in rupture. In the radial fractures operated on, the EPL rupture was caused by chafing against a dorsal plate (n = 2) or wear against the pins of an external fixator (n = 2). Six patients were taking steroids for systemic diseases and in two cases a local steroid injection was given just before the rupture. We conclude that previous injury is the most common cause of rupture of the EPL. but that rheumatoid arthritis or local or systemic steroids, or both, are also important aetiological factors. Seven patients had an iatrogenic cause for their rupture.
15004696 Interleukin-17: a mediator of inflammatory responses. 2004 Mar Interleukin-17 (IL-17) is a prototype member of a new cytokine family with six species identified to date. IL-17 is secreted mainly by activated CD4(+) and CD8(+) T lymphocytes, while its receptor is distributed ubiquitously. IL-17 has been classified as a proinflammatory cytokine because of its ability to induce the expression of many mediators of inflammation, most strikingly those that are involved in the proliferation, maturation and chemotaxis of neutrophils. Increased levels of IL-17 have been associated with several conditions, including airway inflammation, rheumatoid arthritis, intraperitoneal abscesses and adhesions, inflammatory bowel disease, allograft rejection, psoriasis, cancer and multiple sclerosis. This review provides an overview of IL-17 activities, concentrating on those that lead to neutrophil recruitment.
14746811 Inducible nitric oxide synthase activation by interleukin-17. 2004 Feb Interleukin-17 (IL-17) is a proinflammatory T cell cytokine presumably involved in physiological responses to infection, but also in immunopathology of autoimmune disorders such as rheumatoid arthritis. The proinflammatory action of IL-17 depends considerably on its ability to trigger the expression of inducible nitric oxide (NO) synthase (iNOS), an enzyme responsible for the generation of cytotoxic and immunoregulatory free radical NO. Here we discuss the role of IL-17 in the cytokine network controlling iNOS expression, and analyze signaling pathways employed by IL-17 for the initiation of iNOS gene transcription. We also propose biological consequences of IL-17-mediated NO release that could be relevant for the mechanisms or therapy of autoimmune and inflammatory disorders.
14635403 [A case of pseudoscleroderma as paraneoplastic syndrome due to carcinoma of cervical uteri 2003 Oct A 65-year-old female began experiencing arthralgia, morning stiffness and psychroesthesia in April 2000. She visited a rheumatologist and was suspected of having early-stage rheumatoid arthritis. She was referred to our hospital, and was admitted in December 2000. At that time, sclerosis of the skin was advanced, and Raynaud's phenomenon was confirmed. The patient also exhibited nailfold bleeding, and was diagnosed as having systemic scleroderma. She visited a gynecologist for screening and cervical uteri carcinoma was confirmed. She underwent surgery in March 2001, and subsequently, sclerosis in her skin was almost stopped. We believe that these clinical symptoms were related to paraneoplastic syndrome. We therefore immunochemically investigated the pathogenesis of paraneoplastic syndrome and found that connective tissue growth factor (CTGF) might be involved and transforming growth factor-beta (TGF-beta) might not be involved in this case.
14612967 Relationship between peroxyl radical scavenging capability measured by the chemiluminescen 2003 Dec Oxygen-related free radicals have been suggested as a cause of aging and various diseases, for example, various cancers and rheumatoid arthritis. Because of this a radical scavenger as an antioxidant has been sought in food materials. Soy sauce is a traditional fermented seasoning of East Asian countries and is available throughout the world. The relationship between the peroxyl radical scavenging capability using the luminol chemiluminescence method and melanoidin, the main product from aminocarbonylation, i.e., Maillard reaction, from soy sauce was examined. In this study, we report that soy sauce has a very high antioxidative capacity and from the comparisons of the IC50 values of 26 soy sauces in the case of the optical density of the soy sauce's color being standardized, it was found that not only melanoidin is an antioxidative product, but also other products have strong antioxidative properties.
12833654 CDP-870. Celltech/Pfizer. 2003 May Celltech Group plc (formerly Celltech Chiroscience), in collaboration with Pfizer Inc (formerly Pharmacia Corp), is developing CDP-870, a polyethylene glycol (PEG)ylated anti-TNF antibody fragment, for the potential treatment of certain autoimmune and inflammatory diseases, including rheumatoid arthritis (RA) and Crohn's disease (CD). In October 2002, Pharmacia initiated phase III trials for RA and at this time Celltech anticipated initiating phase III trials for CD in mid-2003.
12649849 [Five cases of acute hemorrhagic rectal ulcer in aged patients]. 2003 Jan We report our experience with five cases of acute hemorrhagic rectal ulcer in aged patients. The patients included two men and three women whose ages ranged from 73 to 86 with a mean of 79.6. All cases had underlying disorders, including cerebral vascular disease, fracture of the fibula, senile dementia, chronic rheumatoid arthritis, or were recuperating from a cardiovascular operation. All cases were in bed rest and complained of sudden anal bleeding without pain. Endoscopic examination showed rectal ulcer localized in the lower rectum close to the dentate line. Four cases were treated by HSE injection and ligation by clipping devices with endoscopy and one case was surgically ligated by a transanal approach. All cases had good outcomes. Emergency colonoscopic examination is considered essential for the diagnosis and treatment of acute hemorrhagic rectal ulcers, especially in aged patients with severe underlying disorders.
12641775 Cutaneous vasculitis: a review. 2003 Mar As the skin is commonly involved in systemic vasculitic disorders as well as those hypersensitivity states whose expression is largely skin-confined, cutaneous vasculitic lesions offer a window to diagnosis and a ready source of accessible tissue for biopsy. In this review, we discuss the pathologic manifestations of chronic vasculitic syndromes such as granuloma faciale and erythema elevatum diutinum; IgA-associated vasculitis including Henoch-Schonlein purpura; vasculitis seen in the setting of cryoglobulinemia and hypergammaglobulinemia of Waldenstrom, hereditary deficiencies of complement, and IgA deficiency; those leukocytoclastic vasculitides resulting from hypersensitivity reactions to drug, chemical and foodstuff ingestion; and those vasculitides seen in patients with systemic diseases such as polyarteritis nodosa, rheumatoid arthritis, mixed connective tissue disease, systemic lupus erythematosus, Sjogren's syndrome, relapsing polychondritis, Behcet's disease, Wegener's granulomatosis, and allergic granulomatosis of Churg and Strauss.
12211408 ONO-6818 Cortech/Ono. 2002 Aug ONO-6818 (CP-955) is the lead compound in a series of orally bioavailable neutrophil elastase inhibitors licensed from Cortech and under investigation by Ono for the potential treatment of inflammatory conditions, such as rheumatoid arthritis, inflammatory bowel disease and chronic obstructive pulmonary disease (COPD) [174095]. ONO-6818 was in phase I studies for COPD in Japan as of December 1999 [366431]. Phase I trials for this indication in Japan and the US were ongoing in September 2001 [368565], [422782], [446138]. As of June 2002, however, a number of unconfirmed reports stated that the compound had moved into phase II trials in Japan and was in preparation for phase II trials in the US [456596], [456597].