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ID PMID Title PublicationDate abstract
17317489 Psoriasis, innate immunity, and gene pools. 2007 Mar Recently, emphasis has shifted from T cells to innate (natural) immunity as the possible major culprit in psoriasis. All known elements of innate immune responses are up-regulated in psoriasis lesions, which must have a polygenetic origin. We hypothesize that urbanized populations have been under evolutionary pressure that selects for increased innate immunity responses because those offer relative but immediate protection from epidemic infections. That would have resulted in a changing gene pool, in which alleles of polymorphisms associated with increased innate immunity responses have amplified in these populations. Having too many of these genes together in one individual would result in a relatively low number of infections. On the other hand, it would also result in a higher prevalence of diseases related to increased innate immunity, such as psoriasis, and perhaps also multiple sclerosis and rheumatoid arthritis. Indeed, in indigenous people (Inuit, Aborigines, Ami) who have not been under this selection pressure, morbidity due to infections is high and the prevalence of psoriasis is low or even absent.
17315772 Developments in shoulder arthroplasty. 2007 Jan Indications for shoulder arthroplasty are numerous, mainly owing to glenohumeral osteoarthritis, rheumatoid arthritis, or fracture of the proximal humerus. However, the anatomy and the biomechanics of the shoulder are complex and shoulder arthroplasty has evolved significantly over the past 30 years. This paper presents the main recent evolutions in shoulder replacement, the questions not answered yet, and the main future areas of research. The review focuses firstly on the design, positioning, and fixation of the humeral component, secondly on the design, positioning, and fixation of the glenoid implant, and thirdly on other concepts of shoulder arthroplasty such as the reversed prosthesis, the cementless surface replacement arthroplasty, and the bipolar arthroplasty. This review demonstrates that more research is needed. Although, in the long term, large randomized trials are needed to settle the fundamental questions of what type of replacement and which kind of fixation should be used, biomechanical research in the laboratory should be focused primarily on the comprehension of glenoid loosening, which is a major cause of total shoulder arthroplasty failure, and the significance of radiolucent lines which are often seen but with no clear understanding about their relation with failure.
16891930 Basic science for the clinician 39: NF-kappaB-function, activation, control, and consequen 2006 Aug Were there to be a crossroads through which all inflammatory signaling passed, controlling that junction would provide the ultimate therapeutic target for rheumatoid arthritis and many, if not all, autoimmune diseases. It now seems likely that no single cytokine or cytokine family represents such a crucial nexus. However, there is reason to believe that there may be an intracellular bottleneck that does: the family of NF-kappaB proteins. This family of proteins allows cytokine-receptor signals to enter the nucleus and either enhance or suppress the transcription of many genes involved in inflammation and in cellular survival itself. The same set of proteins is also involved in apoptosis and likely in carcinogenesis. The delicate choreography of control systems, balancing the effects of NF-kappaB proteins on the multiple DNA sites that are targeted, is also a prime target for specific therapies. Moreover, the NF-kappaB system interdigitates with other intracellular systems, eg, kinases, ubiquitin-associated protein degradation, that are critical to the normal function of cells, involved in homeostasis and inflammation, in autoimmune diseases and malignancy.
16463612 [The mechanism of action of cannabis and cannabinoids]. 2006 Jan 21 The effect ofcannabis can be explained on the basis of the function of the cannabinoid receptor system, which consists of CB receptors (CB1, CB2), endoligands to activate these receptors and an enzyme--fatty acid amidohydrolase--to metabolize the endoligands. The endoligands of the cannabinoid receptor system are arachidonic acid-like substances, and are called endocannabinoids. Indications exist that the body also contains arachidonic acid-like substances that inhibit fatty acid amido hydrolase. Various cannabinoids have diverse effects on the receptors, functioning as agonists, antagonists or partial antagonists, as well as affecting the vanilloid receptor. Many known effects ofcannabis can be explained on the basis of this mechanism of action as can the use ofcannabis in various conditions including multiple sclerosis, Parkinson's disease, glaucoma, nausea, vomiting and rheumatoid arthritis.
18332104 DEK is a poly(ADP-ribose) acceptor in apoptosis and mediates resistance to genotoxic stres 2008 May DEK is a nuclear phosphoprotein implicated in oncogenesis and autoimmunity and a major component of metazoan chromatin. The intracellular cues that control the binding of DEK to DNA and its pleiotropic functions in DNA- and RNA-dependent processes have remained mainly elusive so far. Our recent finding that the phosphorylation status of DEK is altered during death receptor-mediated apoptosis suggested a potential involvement of DEK in stress signaling. In this study, we show that in cells committed to die, a portion of the cellular DEK pool is extensively posttranslationally modified by phosphorylation and poly(ADP-ribosyl)ation. Through interference with DEK expression, we further show that DEK promotes the repair of DNA lesions and protects cells from genotoxic agents that typically trigger poly(ADP-ribose) polymerase activation. The posttranslational modification of DEK during apoptosis is accompanied by the removal of the protein from chromatin and its release into the extracellular space. Released modified DEK is recognized by autoantibodies present in the synovial fluids of patients affected by juvenile rheumatoid arthritis/juvenile idiopathic arthritis. These findings point to a crucial role of poly(ADP-ribosyl)ation in shaping DEK's autoantigenic properties and in its function as a promoter of cell survival.
16717113 Autoimmune arthritis associated with mutated interleukin (IL)-6 receptor gp130 is driven b 2006 Jun 12 Mice homozygous for the F759 mutation in the gp130 interleukin (IL)-6 receptor subunit have enhanced gp130-mediated signal transducer and activator of transcription (STAT)3 activation and spontaneously developed a lymphocyte-mediated rheumatoid arthritis-like joint disease. Here, we show that the development of the disease is dependent on both major histocompatibility complex (MHC) II-restricted CD4+ T cells and IL-6 family cytokines. In spite of the necessity for CD4+ T cells, the gp130 mutation was only required in nonhemtopoietic cells for the disease. The gp130 mutation resulted in enhanced production of IL-7. Conditional knockout of STAT3 in nonlymphoid cells showed that the enhancement of IL-7 production was dependent on STAT3 activation by IL-6 family cytokines. Homeostatic proliferation of CD4+ T cells was enhanced in gp130 mutant mice and acceleration of homeostatic proliferation enhanced the disease, whereas the inhibition of homeostatic proliferation suppressed the disease. Anti-IL-7 antibody treatment inhibited not only the enhanced homeostatic proliferation, but also the disease in gp130 mutant mice. Thus, our results show that autoimmune disease in gp130 mutant mice is caused by increased homeostatic proliferation of CD4+ T cells, which is due to elevated production of IL-7 by nonhematopoietic cells as a result of IL-6 family cytokine-gp130-STAT3 signaling.
19080987 [Infectious risk]. 2008 Jul Biological therapies for immune based chronic inflammatory diseases, especially cytokine inhibitors such as TNF-alpha antagonists, have been acceptably well tolerated in clinical trials with patients suffering rheumatic, dermatologic and intestinal diseases in which they have been subsequently indicated. However, the pharmacovigilance studies and long-term follow-up have clarified several aspects on their safety in the everyday clinical use. The adverse effects associated with TNF-alpha inhibitors can generally be classified into those related to the target (or class) and those related to the agent. Target-related adverse events include those potentially attributable to the immunosuppression inherent in blocking a key cytokine, a phenomenon that could increase the susceptibility to infections and neoplasms. Specific inhibition of TNF-alpha could also facilitate hepatotoxicity, production of autoantibodies, development of demyelinizing diseases and it is also possibly associated to the worsening of congestive heart failure. The side effects related to the agent itself, such as allergic reactions and immunogenicity, are idiosyncratic phenomena of each molecule. Infliximab is an IgG1 class chimeric monoclonal antibody with extensive accumulated experience in the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, intestinal inflammatory disease and, recently, moderate-to-severe plaque psoriasis. It is also being evaluated in other inflammatory dermatitis and systemic diseases with skin expression, such as severe atopic dermatitis, pityriasis rubra pilaris, pyoderma gangrenosum, cutaneous sarcoidosis, Adult Still's disease, inverted acne and refractory graft -versus- host disease. Predisposition of infliximab-treated individuals, as occurs with other anti-TNF-alpha agents, to cause an increase of conventional pyogenic infections (of the skin and soft tissues, respiratory tract, genitourinary tracts and bacteriemias) and an increase in granulomatous and opportunistic infections due to invasive or intracellular pathogens (such as Mycobacterium tuberculosis), has been well established and quantified in the last five years. We presently know that the initiation of screening strategies of latent infections (especially tuberculosis) in the host candidate to receive anti-TNF-alpha drugs, with their corresponding early treatment to avoid reactivations, and other prophylaxis, hygiene and vaccination measures have not only minimized these risks of suffering infections but also have practically reduced and equalized the different capacity to trigger infections belonging to each one of the biological agents individually.
17101059 Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A3 ad 2006 Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A3 adenosine receptor (A3AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A3AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A3AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A3AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A3AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A3AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A2AAR and A3AR over-expression in paw cells from treated animals. Moreover, increased A3AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A3AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A3AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA.
18925441 [Is fibromyalgia a neurological disease?]. 2008 Nov The key feature of fibromyalgia is a chronic pain picture located in different structures of the musculoskeletal system, but without any evidence of disease in them. Besides pain, patients with fibromyalgia often describe tiredness, sleep disorders, headache, and emotional problems, as well as many other psychosomatic complaints. Genetic and environmental factors have been implied in the pathogenesis of fibromyalgia, its perpetuation being explained by an alteration of the nociceptive system, thus leading to a neuroendocrine syndrome of chronic stress. Although research has provided a significant amount of data, there is no definite biomarker for fibromyalgia so far. The disease can appear alone or associated, among other diseases, with rheumatoid arthritis, erythematous systemic lupus, myopathies and multiple sclerosis. Fibromyalgia generally has very important repercussions on family, social and professional life of the patient, especially considering that therapeutics (aerobic exercise, antidepressants and antiepileptic drugs) have hardly shown any effectiveness. However, achieving a precise diagnosis, being able to transmit it to patients in a realistic way, along with attaining an optimally personalized treatment, are of primary importance, among other things, in order to reduce possible iatrogenesis caused from an individual viewpoint in a problem with multiple aspects.
20046709 Development of fast dispersible aceclofenac tablets: effect of functionality of superdisin 2008 Mar Aceclofenac, a non-steroidal antiinflammatory drug, is used for posttraumatic pain and rheumatoid arthritis. Aceclofenac fast-dispersible tablets have been prepared by direct compression method. Effect of superdisintegrants (such as, croscarmellose sodium, sodium starch glycolate and crospovidone) on wetting time, disintegration time, drug content, in vitro release and stability parameters has been studied. Disintegration time and dissolution parameters (t(50%) and t(80%)) decreased with increase in the level of croscarmellose sodium. Where as, disintegration time and dissolution parameters increased with increase in the level of sodium starch glycolate in tablets. However, the disintegration time values did not reflect in the dissolution parameter values of crospovidone tablets and release was dependent on the aggregate size in the dissolution medium. Stability studies indicated that tablets containing superdisintegrants were sensitive to high humidity conditions. It is concluded that fast-dispersible aceclofenac tablets could be prepared by direct compression using superdisintegrants.
19740070 Multisegmental foot modeling: a review. 2008 Over the past two decades, a number of multisegmental foot models have been developed in order to characterize foot kinematics. This paper reviews methods of multisegmental foot modeling, technical elements of the models, select clinical applications of the models, and future directions in this area of research. Technical areas discussed include angular derotation mechanisms and capture technology. Models discussed address two-, three-, four-, five-, and nine-segment approaches. Additional models which address foot segments using other definitions, are also discussed. Clinical applications of multisegmental foot models include pathologic gait characterization in rheumatoid arthritis, posterior tibial tendon dysfunction, and hallux rigidus. Areas of continued development, including soft tissue artifact and nomenclature, are also discussed.
16671329 [A case of drug eruption induced by hydroxyzine pamoate]. 2006 Jan A 62-year-old woman with rheumatoid arthritis, Basedow's disease and arrhythmia has been treated with antirheumatic, antiarrhythmic drugs and so on. She developed pruritic diffuse erythema with papules on the trunk and extremities 2 days after taking hydroxyzine pamoate for asteatotic eczema. Laboratory data showed increased levels of eosinophils. Histopathological examination revealed a infiltrate of inflammatory cells in the upper dermis. Patch tests with hydroxyzine pamoate and hydroxyzine hydrochloride were positive. From these findings, we diagnosed this case as drug eruption due to hydroxyzine. Her eruption subsided after she discontinued hydroxyzine pamoate and other drugs which were started within 5 days before the onset of the eruption and was treated with systemic steroid, systemic antiallergic drug and topical steroid.
18700175 Vaccination and autoimmune rheumatic diseases. 2008 Dec Patients with autoimmune rheumatic diseases are at increased risk of developing infections. However, concerns about the safety and the immunogenicity of vaccines in these patients limited their use. Most of the data against the use of vaccines come from the reported cases of previously healthy individuals who presented the onset of rheumatic diseases after immunization, nevertheless a causal relationship has not been established. During the past few decades influenza and pneumococcal vaccines, administered to patients with systemic lupus erythematosus, were found to be safe and, generally, serologically effective, even though there is the possibility of inadequate response, especially in patients receiving immunosuppressive agents. In patients with rheumatoid arthritis influenza and pneumococcal vaccines can be considered safe and immunogenic in most cases. Treatment with TNFalpha blocking agents did not appear to impair the immune response.
18466518 Application of sequential haplotype scan methods to case-control data. 2007 Haplotype association analysis based on arbitrarily chosen markers might lower statistical power because of the larger number of degrees of freedom caused by irrelevant makers.On the other hand, an exhaustive search for all possible combinations of markers for haplotype analysis is computationally expensive for genome-wide association analysis.To improve power, we applied our recently developed sequential haplotype scan method to case-control data for rheumatoid arthritis, including the PTPN22 candidate gene on chromosome 1p and the association mapping data on chromosome 18q, from the Genetic Analysis Workshop 15. The results showed that our new approach is at least as powerful as the traditional single-locus analysis and sometimes can be more powerful.
18466505 Pattern-based mining strategy to detect multi-locus association and gene x environment int 2007 As genome-wide association studies grow in popularity for the identification of genetic factors for common and rare diseases, analytical methods to comb through large numbers of genetic variants efficiently to identify disease association are increasingly in demand. We have developed a pattern-based data-mining approach to discover unlinked multilocus genetic effects for complex disease and to detect genotype x phenotype/genotype x environment interactions. On a densely mapped chromosome 18 data set for rheumatoid arthritis that was made available by Genetic Analysis Workshop 15, this method detected two potential two-locus associations as well as a putative two-locus gene x gender interaction.
18269091 Ginger: an ancient remedy and modern miracle drug. 2007 Dec Ginger has been used safely for thousands of years in cooking, and medicinally in folk and home remedies. Advanced technology enables the validation of these traditional experiences. The National Center for Complementary and Alternative Medicine (NCCAM) has evaluated the results of the available studies, rating the reports from "suggestive" (for short-term use of Ginger for safe relief from pregnancy related nausea and vomiting), to "mixed" (when used for nausea caused by motion sickness, chemotherapy, or surgery), and to "unclear" for treating rheumatoid arthritis, osteoarthritis, or joint and muscle pain). NCCAM has funded investigators to study interactions of ginger with drugs (immunosuppressants), its effect of reducing nausea in patients receiving chemotherapy, and the safety and effectiveness of its use for health purposes, as well as its impact on inflammation. Upon completion of these studies, the scope of ginger's use will be clearly identified and incorporated into mainstream therapeutic options, thereby integrating east and west, old with new, to render ginger as a true "Universal Remedy".
17989950 [Arthroscopy of the elbow joint]. 2007 Nov Clear indications have been recognised for arthroscopic surgery of the elbow since the 1980s. Good indications are loose bodies, mild or moderate restriction of the range of movement and early stages of rheumatoid arthritis. Cartilage diseases such as Panner disease or focal radial chondropathy can be treated by arthroscopic debridement and microfracturing. Impingement syndromes affecting the lateral compartment of the joint respond well to resection of synovial plicae. The technical demands of endoscopic arthrolysis procedures for joints with mild or moderate restriction of range of movement are extremely heavy; only experienced surgeons should operate on such patients. Arthroscopy of the elbow joint should be carried out only by operators who have already gained experience in other joints, because of the close relations of nerves and vessels in the elbow. A rigorous standard should be followed in planning the procedure and in creation of the portals and performance of the diagnostic round-up in the joint, to make it possible to work purposefully and quickly, and thus with minimum complications.
17970893 Off-label uses of rituximab in dermatology. 2007 Jul Since its approval in 1997 by the FDA, rituximab has been approved for use in certain B-cell lymphomas and treatment-resistant rheumatoid arthritis. Over the past 10 years, many case reports have indicated rituximab's efficacy in a number of inflammatory conditions in dermatology. This article includes a review of the mechanism of action, dosing, and side effect profile, as well as a review of the current literature on off-label uses of the CD20(+) B-cell antagonist rituximab.
17685049 Radiofrequency excision of a large postcricoid mucous cyst. 2007 OBJECTIVES: To present the case of a patient with a large mucous cyst originating from the postcricoid region that was removed by radiofrequency excision. METHODOLOGY: A 75-year-old male who complained of progressive difficulty in breathing, dysphonia, and throat discomfort upon swallowing presented at our clinic. Computerized tomography imaging showed a 4 x 4 x 3 cm cystic mass in the hypopharyngeal region. The patient had been on medical therapy for rheumatoid arthritis for 25 years, and his ability to extend his neck was totally restricted. Thus, the Kleinsasser operating laryngoscope could not be inserted; instead, the blade of a flexible intubation laryngoscope and a 30 degree rigid nasal endoscope was used to visualize the lesion. RESULT: The walls of the cyst were excised from the postcricoid region using a radiofrequency device to avoid bleeding. CONCLUSION: Radiosurgery of these kinds of lesions produces less hemorrhage and may provide a suitable alternative to classical surgery.
17501702 11th annual Inflammatory and Immune Diseases Drug Discovery and Development Summit 12-13 M 2007 Jun The Strategic Research Institute (SRi) hosted the 11th International Inflammation and Immune Diseases Drug Discovery and Development World Summit in San Francisco during 12-13 March 2007. The summit comprised keynote sessions and two parallel tracks and focussed on targeting mechanisms for drug discovery and development, which modulate the immune response and which have anti-inflammatory activity in a number of human diseases. Indications included psoriasis, hepatitis C, allergic dermatitis, systemic lupus erythematosus, rheumatoid arthritis and osteoarthritis, multiple sclnerosis, cardiovascular disease and asthma. Data were presented supporting all stages of drug discovery from target identification and validation through to lead identification and optimisation to both early- and late-stage clinical development.