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ID PMID Title PublicationDate abstract
18075793 The genetics and biology of Irf5-mediated signaling in lupus. 2007 Dec Recently much attention was attracted to the importance of the type I interferon pathway in the initiation and development of the autoimmune disease systemic lupus erythematosus (SLE). Many SLE patients have increased serum levels of IFN-alpha and display an IFN gene expression "signature" characterized by strong overexpression of IFN-responsive genes in leukocytes and target tissues. Moreover, about 20% of cancer patients treated with IFN-alpha therapy manifest symptoms resembling SLE and some later develop the disease. One of the key genes of the IFN-alpha pathway, IRF5, was found to be strongly associated with SLE. Two functional SNPs lead to alternative splicing and altered steady-state level of IRF5 gene expression. Besides, the gene has a polymorphic inserion/deletion in exon 6, which contributes to the diversity in the isoform pattern of IRF5. Interestingly, recent studies have not found association of IRF5 with the other autoimmune diseases, such as rheumatoid arthritis or psoriasis, suggesting the unique role for IRF5 in the development of lupus. Here, we present the current knowledge on IRF5 genetics and its biological function and discuss the possible ways in which IRF5 contributes to susceptibility to SLE.
18040109 Occipitocervical contoured rod stabilization: does it still have a role amidst the modern 2007 Oct BACKGROUND: The occipitocervical contoured rod (CR) stabilization for use in craniovertebral junction (CVJ) pathologies is an effective and economical technique of posterior fusion (PF). AIMS: The various indications for CR in CVJ pathologies are discussed. SETTINGS AND DESIGN: Retrospective analysis. MATERIALS AND METHODS: Fifty-four patients (mean age: 31.02+/-13.44 years; male: female ratio=5.75:1) who underwent CR stabilization are included. The majority had congenital atlantoaxial dislocation (AAD; n=50); two had CVJ tuberculosis; one each had rheumatoid arthritis and C2-3 listhesis, respectively. The indications for CR fusion in congenital AAD were associated Chiari 1 malformation (C1M) (n=29); occipitalized C1 arch and/or malformed or deficient C1 or C2 posterior elements (n=9); hypermobile AAD (n=2); and, rotatory AAD (n=3). Contoured rod as a revision procedure was also performed in seven patients. Most patients were in poor grade (18 in Grade III [partial dependence for daily needs] and 15 in Grade IV [total dependence]); 15 patients were in Grade II [independent except for minor deficits] and six in Grade I [no weakness except hyperreflexia or neck pain]. RESULTS: Twenty-four patients improved, 18 stabilized and six deteriorated at a mean follow-up (FU) of 17.78+/-19.75 (2-84) months. Six patients were lost to FU. In 37 patients with a FU of at least three months, stability and bony union could be assessed. Thirty-one of them achieved a bony fusion/stable construct. CONCLUSIONS: Contoured rod is especially useful for PF in cases of congenital AAD with coexisting CIM, cervical scoliosis, sub-axial instability and/or asymmetrical facet joints. In acquired pathologies with three-column instability, inclusion of joints one level above the affected one by using CR, especially enhances stability.
17994363 In vitro and ex vivo permeation studies of etodolac from hydrophilic gels and effect of te 2007 Oct Etodolac, a highly lipophilic anti-inflammatory drug, is widely used in rheumatoid arthritis usually at an oral dose of 200 mg twice daily. The commonest side effects during therapy with etodolac is generally gastrointestinal disturbances these are usually mild and reversible but in some patients are peptic ulcer and severe gastrointestinal bleeding. To eliminate these side effects and obtain high drug concentration at the application side, dermal application of etodolac seems to be an ideal route for administration. Hydrophilic gel formulations of etodolac were prepared with carboxymethylcellulose sodium. The effect of different terpenes (anethole, carvacrol, and menthol) as an enhancer on the percutaneous absorption of etodolac was also investigated. Permeation studies were carried out with unjacketed modified horizontal diffusion cells through cellulose membrane and rat skin. In vitro studies with cellulose membrane showed that all formulations presented the same drug release profile (p > 0.05). Ex vivo studies with excised rat skin revealed that etodolac was released and penetrated into rat skin quickly. Anethole, a hydrophobic terpene, enhanced the absorption of etodolac significantly (p < 0.05). This result is consistent with the fact that hydrophobic terpenes are effective on the percutaneous absorption of lipophilic drugs. Menthol and carvacrol, hydrophilic terpenes, did not enhance the absorption of etodolac. The lipophilicity of the enhancers seems an important factor in promoting penetration of etodolac through the skin. Since etodolac creates gastrointestinal disturbances, topical formulations of etodolac in gel form including 1% anethole could be an alternative.
17939102 Inhibition of 5-lipoxygenase product synthesis by natural compounds of plant origin. 2007 Oct The biosynthesis of leukotrienes (LTs) is initiated by the transformation of free arachidonic acid to LTA (4) by 5-lipoxygenase (5-LO). Subsequent enzymatic conversion of LTA (4) yields LTB (4) and the cysteinyl-LTs C (4), D (4) and E (4). LTs have prominent functions in pathophysiology and are connected to numerous disorders including bronchial asthma, allergic rhinitis, inflammatory bowel and skin diseases, rheumatoid arthritis, cancer, osteoporosis and cardiovascular diseases. Pharmacological and genetic interruption of the 5-LO pathway or blockade of LT receptors, serving as means for intervention with LTs, may be of therapeutic value for certain related disorders. Natural or plant-derived substances were among the first 5-LO inhibitors identified in the early 1980 s. To date, a huge number of diverse plant-derived compounds have been reported to interfere with 5-LO product synthesis. However, many investigations have addressed the efficacy of a given compound solely in cellular test systems and analysis of direct interference with 5-LO has been neglected. In the first part of this review, the biology and molecular pharmacology of the 5-LO pathway is summarized in order to understand its overall regulation and complexity as well as to comprehend the possible points of attack of compounds that eventually lead to inhibition of 5-LO product formation in intact cells. In the second part, natural compounds that interfere with 5-LO product formation are compiled and grouped into structural classes, and the underlying molecular mechanisms and structure-activity relationships are discussed.
17868652 The interplay between viruses and innate immune signaling: recent insights and therapeutic 2008 Feb 1 The immediate response to viral infection relies on pattern-recognition receptors (PRRs), most prominently the Toll-like receptors (TLRs) and the RNA helicases RIG-I and MDA5, as well as double stranded RNA-dependent protein kinase (PKR) and the DNA receptor, DAI. These PRRs recognize pathogen-associated molecular patterns (PAMPs) such as viral proteins and nucleic acids. The engagement of these receptors then initiates intracellular signaling cascades which ultimately cause the activation of transcription factors and the expression of type I interferons and pro-inflammatory cytokines. This innate response establishes an anti-viral state in the infected cell and its neighbours and alerts immune cells to the danger. In order to establish a productive infection, viruses need to overcome this initial anti-viral response. Evasion of innate immune defences is achieved by means of viral proteins that inhibit the signaling cascades emanating from the PRRs. The same innate signal transduction pathways have been implicated in conditions of sterile inflammation, such as rheumatoid arthritis and multiple sclerosis, and in autoimmunity. Because viral proteins target crucial host proteins involved in these pathways, they can point the way to key drug targets. Further, the viral proteins themselves or derivatives of them may be of use therapeutically to curtail inflammation and autoimmunity.
17697150 Enzyme-linked immunosorbent assay using multimers of the 16th non-collagenous domain of th 2007 Sep Bullous pemphigoid (BP) and pemphigoid gestationis (PG) are acquired autoimmune subepidermal blistering diseases characterized by autoantibodies against the hemidesmosomal proteins BP180/type XVII collagen and BP230. In the vast majority of BP and PG patients, these autoantibodies bind to epitopes clustered within the 16th non-collagenous domain of BP180. An ELISA system for the detection of these autoantibodies was developed and evaluated using 16th non-collagenous domain (NC16A) tetramers instead of monomers. In contrast to antigens fused to large proteins used in the past for the detection of autoantibodies against type XVII collagen, tetrameric antigen fragments bearing a small hexahistidine tag allow for high expression levels without the need to cleave off the fusion partner. Using tetrameric BP180 NC16A, positive reactions were found in 106 (89.8%) of 118 randomly selected BP sera and in all of 20 (100%) randomly selected PG sera, whereas only 2.2% of a large cohort of control subjects were positive in this assay, including patients with rheumatoid arthritis (two of 107), progressive systemic sclerosis (two of 50), systemic lupus erythematosus (one of 72), and healthy blood donors (10 of 494). Thus, the sensitivity and specificity of the new anti-tetrameric NC16A ELISA were 89.9% and 97.8% respectively. Levels of circulating autoantibodies against BP180 paralleled disease activity in the pemphigoid patients. In conclusion, the use of tetrameric NC16A in ELISA results in a sensitive and specific tool for diagnosis and monitoring of BP and PG.
17414323 Resting B cells suppress tumor immunity via an MHC class-II dependent mechanism. 2007 Apr Resting B cells have been variously shown to induce direct tolerance of antigen specific CD8+ T cells, induce T-cell anergy via transforming growth factor-beta production, down-regulate interleukin-12 production by dendritic cells (DC) and influence TH1/TH2 differentiation via the production of regulatory cytokines. Through these mechanisms, B cells can exert a regulatory function in in vivo models of T-cell immunity including, experimental autoimmune encephalitis and rheumatoid arthritis. Here, we show that the resting B cells inhibit the ability of DC vaccination to provide protection from tumor growth. Inhibition of DC induced immunity by B cells was independent of presentation of major histocompatibility molecule (MHC) class-I bound tumor antigen but dependent on B-cell expression of MHC class-II. Administration of B cells did not alter the ability of DC to migrate from the injection site or impair DC-T cell interactions within the draining lymph node. The inhibitory effect of B cells was lost when they were activated by CD40L and partially reversed by the depletion of CD4+/CD25+ regulatory T cells. Together our findings indicate that the resting B cells are capable of limiting CD8+ T-cell effector function induced by DC vaccination via a mechanism that is dependent on the expression of MHC class-II molecules.
17305324 Discovery of Ecopladib, an indole inhibitor of cytosolic phospholipase A2alpha. 2007 Mar 22 The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A2alpha (cPLA2alpha, type IVA phospholipase) are described. Inhibitors of cPLA2alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed. Compound 123 (Ecopladib) is a sub-micromolar inhibitor of cPLA2alpha in the GLU micelle and rat whole blood assays. Compound 123 displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models.
17167792 Therapeutic potential of the chemokine receptor CXCR4 antagonists as multifunctional agent 2007 The chemokine receptor CXCR4 possesses multiple critical functions in normal and pathologic physiology. CXCR4 is a G-protein-coupled receptor that transduces signals of its endogenous ligand, the chemokine CXCL12 (stromal cell-derived factor-1, SDF-1). The interaction between CXCL12 and CXCR4 plays an important role in the migration of progenitors during embryologic development of the cardiovascular, hemopoietic, central nervous systems, and so on. This interaction is also known to be involved in several intractable disease processes, including HIV infection, cancer cell metastasis, leukemia cell progression, rheumatoid arthritis (RA), and pulmonary fibrosis. It is conjectured that this interaction may be a critical therapeutic target in all of these diseases, and several CXCR4 antagonists have been proposed as potential drugs. Fourteen-mer peptides, T140 and its analogues, were previously developed in our laboratory as specific CXCR4 antagonists that were identified as HIV-entry inhibitors, anti-cancer-metastatic agents, anti-chronic lymphocytic/acute lymphoblastic leukemia agents, and anti-RA agents. Cyclic pentapeptides, such as FC131 [cyclo(D-Tyr-Arg-Arg-L-3-(2-naphthyl)alanine-Gly)], were also previously found as CXCR4 antagonist leads based on pharmacophores of T140. This review article describes the elucidation of multiple functions of CXCR4 antagonists and the development of a number of low-molecular weight CXCR4 antagonists involving FC131 analogues and other compounds with different scaffolds including linear-type structures.
17064780 Copper chelating anti-inflammatory agents; N1-(2-aminoethyl)-N2-(pyridin-2-ylmethyl)-ethan 2007 Jan An in vitro and in vivo study of some copper chelating anti-inflammatory agents for alleviation of inflammation associated with rheumatoid arthritis (RA) has been conducted. Two copper chelating agents, N(1)-(2-aminoethyl)-N(2)-(pyridin-2-ylmethyl)ethane-1,2-diamine ([555-N]) and N-(2-(2-aminoethylamino)ethyl)picolinamide ([H(555)-N]) have been synthesized as their hydrochloride salt; their protonation constants and formation constants with Cu(II), Zn(II) and Ca(II) determined by glass electrode potentiometry at 298K and an ionic strength of 0.15M. Cu(II) formed stable complexes at physiological pH while the in vivo competitors, Zn(II) and Ca(II) formed weak complexes with both chelating agents. Both [555-N] and [H(555)-N] showed better selectivity for Cu(II) than for Zn(II) and Ca(II). Electronic spectra for species formed at physiological pH suggest a square planar geometry. Speciation calculations using a blood plasma model predicted that these copper chelating agents are able to mobilize Cu(II) in vivo, while bio-distribution studies of their (64)Cu(II)-labelled complexes at physiological pH showed tissue accumulation and retention indicating an encouraging biological half life.
16982193 Discovery of small molecule inhibitors of integrin alphavbeta3 through structure-based vir 2006 Nov 15 Inhibitors of integrin alphavbeta3 have been implicated in the treatment of a variety of diseases, including tumor metastasis, neovascularization, osteoporosis, and rheumatoid arthritis. It is therefore desirable to develop new types of small molecule inhibitors of integrin alphavbeta3. Here we describe the discovery of novel classes of small molecule inhibitors, via structure-based virtual screening, that target the ligand binding site of integrin alphavbeta3. Application of the docking procedure for screening of a commercially available compound database resulted in a 1774-fold reduction in the size of the screening set (88695 to 50 compounds) and gave a hit-rate of 14% upon biological evaluation (IC50 value ranging from 30 to 200 microM). The best hit, compound 37, 3,4-dichloro-phenylbiguanide, showed inhibitory activity, in a time- and dose-dependent manner, in both cell motility and angiogenesis assays. Based on the best hit, compound 37, a more effective derivative compound 62 has been identified. Furthermore, molecular graphics analyses of a series of substituted phenylbiguanides were carried out to predict the binding mode between the active compounds and integrin alphavbeta3. Our results indicate that the substituted phenylbiguanides might be involved in the inhibition of bivalent cation-mediated ligand binding of integrin alphavbeta3.
16980722 Cardiac arrhythmias and conduction disturbances in autoimmune rheumatic diseases. 2006 Oct Rhythm and conduction disturbances and sudden cardiac death (SCD) are important manifestations of cardiac involvement in autoimmune rheumatic diseases (ARDs). In patients with rheumatoid arthritis (RA), a major cause of SCD is atherosclerotic coronary artery disease, leading to acute coronary syndrome and ventricular arrhythmias. In systemic lupus erythematosus (SLE), sinus tachycardia, atrial fibrillation and atrial ectopic beats are the major cardiac arrhythmias. In some cases, sinus tachycardia may be the only manifestation of cardiac involvement. The most frequent cardiac rhythm disturbances in systemic sclerosis (SSc) are premature ventricular contractions (PVCs), often appearing as monomorphic, single PVCs, or rarely as bigeminy, trigeminy or pairs. Transient atrial fibrillation, flutter or paroxysmal supraventricular tachycardia are also described in 20-30% of SSc patients. Non-sustained ventricular tachycardia was described in 7-13%, while SCD is reported in 5-21% of unselected patients with SSc. The conduction disorders are more frequent in ARD than the cardiac arrhythmias. In RA, infiltration of the atrioventricular (AV) node can cause right bundle branch block in 35% of patients. AV block is rare in RA, and is usually complete. In SLE small vessel vasculitis, the infiltration of the sinus or AV nodes, or active myocarditis can lead to first-degree AV block in 34-70% of patients. In contrast to RA, conduction abnormalities may regress when the underlying disease is controlled. In neonatal lupus, 3% of infants whose mothers are antibody positive develop complete heart block. Conduction disturbances in SSc are due to fibrosis of sinoatrial node, presenting as abnormal ECG, bundle and fascicular blocks and occur in 25-75% of patients.
16978829 Inhibition of macrophage activation and phagocytosis by a novel NF-kappaB inhibitor, dehyd 2006 Nov Previously, we designed and synthesized a new NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ). In the present research we looked into the effect of DHMEQ on the activation of macrophages, especially on the phagocytotic activity of cells of the mouse macrophage-like cell line RAW264.7. DHMEQ inhibited lipopolysaccharide (LPS)-induced NF-kappaB activation by inhibiting its nuclear translocation from the cytoplasm. It also inhibited the expression of inducible NO synthase (iNOS) and nitric oxide (NO) production induced by LPS and interferon-gamma. Using enzyme-linked immunosorbent assays (ELISAs) we showed DHMEQ to inhibit LPS-induced secretion of IL-6, IL-12, interleukin-1beta (IL-1beta), and TNF-alpha. Furthermore, DHMEQ also inhibited the phagocytosis of fluorescently labeled Escherichia coli by RAW264.7 cells treated with LPS or IL-1beta, thus being the first evidence for the involvement of NF-kappaB in the regulation of phagocytosis by use of this inhibitor. Deletion of p65 by siRNA also inhibited the phagocytosis. DHMEQ inhibited the LPS-induced but not IL-1beta-induced phagocytosis of glass beads, indicating that activation of not only NF-kappaB but also Toll-like receptor 4 (TLR-4) is essential for the phagocytosis of E. coli. Previously we found that DHMEQ inhibited type 2 collagen-induced rheumatoid arthritis and the growth of various human carcinomas in mice. It is thus likely that inhibition of macrophage activation is involved in the mechanism of these anti-inflammatory and antitumor activities of DHMEQ in mice.
16970925 The alternative NF-kappaB pathway from biochemistry to biology: pitfalls and promises for 2006 Oct 30 The past two decades have led to a tremendous work on the transcription factor NF-kappaB and its molecular mechanisms of activation. The nuclear translocation of NF-kappaB is controlled by two main pathways: the classical and the alternative NF-kappaB pathways. The classical NF-kappaB pathway activates the IKK complex that controls the inducible degradation of most IkappaB family members that are IkappaBalpha, IkappaBbeta, IkappaBvarepsilon and p105. The alternative NF-kappaB pathway induces p100 processing and p52 generation through the activation of at least two kinases, which are NIK and IKKalpha. Genetic studies have shown that IKKgamma is dispensable for the alternative pathway, which suggests the existence of an alternative IKKalpha-containing complex. It is noteworthy that activation of particular p52 heterodimers like p52/RelB requires solely the alternative pathway while activation of p52/p65 or p52/c-Rel involves a "hybrid pathway". Among others, LTbetaR, BAFF-R, CD40 and RANK have the ability to induce the alternative pathway. The latter plays some roles in biological functions controlled by these receptors, which are the development of secondary lymphoid organs, the proliferation, survival and maturation of B cell, and the osteoclastogenesis. Exacerbated activation of the alternative pathway is potentially associated to a wide range of disorders like rheumatoid arthritis, ulcerative colitis or B cell lymphomas. Therefore, inhibitors of the alternative pathway could be valuable tools for the treatment of inflammatory disorders and cancers.
16913667 [Clinical aspects of the complement system]. 2006 Jul The complement system consists of more than 30 proteins and has 3 types of activation pathways: classical, lectin and alternative pathways. The complement system not only has a role in innate immunity but also works as an antibody-dependent effecter to eliminate pathogens. It is useful to measure serum levels of CH50, C3 and C4 in patients with immune-mediated diseases. While increased levels of CH50 are associated with non-specific inflammation, decreased levels of CH50 in combination with normal or decreased levels of C3 and C4 are associated with specific immune-mediated diseases. Recent studies have demonstrated that the defect in the clearance of immune complexes and apoptotic cells is associated with autoimmune disease. Mice deficient in Clq show a lupus-like phenotype with the appearance of antinuclear antibodies and glomerulonephritis due to a defect in the clearance of immune complexes and apoptotic cells. This at least explains the paradox that, in humans, deficiency in an early complement component is a major risk factor for SLE. It is demonstrated that mutations in factor H, membrane cofactor protein (MCP) and factor I gene are associated with atypical hemolytic uremic syndrome. Since the complement system is a central mediator of inflammation, it is recognized as a promising therapeutic target. Anti-C5 monoclonal antibody was developed to block the final stage of complement activation. Pexelizumab is a single chain, short-acting anti-C5 antibody and is used for reperfusion after myocardial infarction, or for coronary artery bypass graft surgery with cardiopulmonary bypass. Eculizumab is a long-acting anti-C5 antibody used for paroxysmal nocturnal hemoglobinuria, rheumatoid arthritis, membranous glomerulonephritis with promising results.
16902810 Clinical response is associated with elevated plasma interleukin-1 receptor antagonist dur 2006 Sep Depletion of granulocytes and monocytes (GM) by selective apheresis (GMA) with an Adacolumn exerts an anti-inflammatory effect in patients with ulcerative colitis (UC) or rheumatoid arthritis. However, the mechanism of the anti-inflammatory effect of GMA is not fully understood yet. We investigated the effect of GMA on the plasma concentration of interleukin-1 receptor antagonist (IL-1ra), a potent anti-inflammatory cytokine. Twenty-six patients with active UC received GMA at one session per week for 5 consecutive weeks. Clinical response was defined as Deltaclinical activity index (DeltaCAI=CAI at entry - CAI at post)>or=4, while clinical remission was defined as CAI
16882171 Serum levels of BAFF are increased in bullous pemphigoid but not in pemphigus vulgaris. 2006 Aug BACKGROUND: BAFF [B-cell activating factor belonging to the tumour necrosis factor (TNF) family] is a member of the TNF superfamily that regulates B-lymphocyte proliferation and survival. It has been demonstrated that increased levels of soluble BAFF are associated with systemic autoimmunity in patients with systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome, and in animal models of spontaneous autoimmune diseases. However, the significance of circulating BAFF in autoimmune bullous diseases is unknown. OBJECTIVES: To examine whether BAFF levels are elevated in the autoimmune blistering diseases pemphigus vulgaris (PV) and bullous pemphigoid (BP). METHODS: We examined sera obtained from 21 patients with PV, 39 patients with BP and 22 healthy donors. We performed enzyme-linked immunosorbent assays for soluble BAFF and each disease-specific antibody: antidesmoglein-3 antibody for PV and anti-BP180 antibody for BP. RESULTS: Significant elevations of serum BAFF levels were found in the patients with BP, but not with PV. There was apparently no significant association between the serum BAFF levels and titres of anti-BP180 antibodies in the patients with BP. However, serum BAFF levels tended to be more elevated in patients with a shorter disease duration. There was a tendency that BAFF levels increased before the anti-BP180 antibody levels increased at the onset of BP and quickly decreased in response to treatment. CONCLUSIONS: BAFF may be a useful marker for early activation of an autoimmune diathesis and may play a critical role in triggering activation of self-antigen-driven autoreactive B cells in BP.
16596274 Increased expression of membrane TNF-alpha on activated peripheral CD8+ T cells in systemi 2006 May Membrane TNF-alpha is a precursor form of soluble TNF-alpha and exerts pro-inflammatory functions in a cell-to-cell contact manner. We showed that membrane TNF-alpha is induced upon activation on the cell surface of CD4+ T cells and CD8+ T cells. In patients with systemic lupus erythematosus (SLE), the percentage of membrane TNF-alpha-bearing CD8+ T cells (41.5+/-12.3%) was significantly higher compared with those of healthy controls (26.7+/-3.9%) (p=0.007) or patients with rheumatoid arthritis (29.8+/-15.4%) (p=0.038). Membrane TNF-alpha-bearing CD8+ T cells from SLE patients displayed cytotoxic activity against L929 cells. It is possible that membrane TNF-alpha may be involved in the increased apoptosis and the generation of autoantigens in SLE.
16462212 Clinical study of a modified Brooks technique for atlanto-axial subluxation using polyethy 2006 Feb Forty-four patients, 15 males and 29 females (3-71 years old; mean age, 52.9), were treated for the control of cervical instability with a modified Brooks operation using Tekmilon tape (an ultrahigh molecular weight polyethylene tape) instead of metal wires. Forty of the patients had rheumatoid arthritis (RA) with atlanto-axial subluxation (AAS), three patients had os odontoideum, and one patient had a cervical spine injury. The mean follow-up period was 8 years and 4 months. These patients were divided into three groups: 30 years or less, 31 to 60 years, and over 60 years. Atlanto-dental interval (ADI), inclination angle of atlanto-axial vertebrae (A-A angle), and bone fusion were examined on plain radiographs. The proportion of patients with reduced neck pain (Ranawat's grade 0 or grade 1) increased from 42.5% to 97.9% at the time of postoperative evaluation. Surgical complications, such as dural tear, lamina fracture, and spinal cord injury did not occur in any cases. Thirty-nine patients (88.6%) achieved bone union. ADI in the maximum flexed position improved from 10.3 to 2.5 mm. There was no statistical difference between ADI in males and females. ADI did not change in any age group both before and after surgery. A-A angle also improved from 9.4 to 24.4 degrees. The polyethylene tapes, used for internal fixation, caused no neurologic complications during sublaminar wiring and produced no MR artifacts. This modified Brooks technique using Tekmilon tape was proved to be a simple and safe treatment of AAS.
16369458 Macrophage may responses to androgen via its receptor. 2006 Jan BACKGROUND: Sex hormones have profound effects on immune responses and may influence the disease which caused by intracellular parasite(Leishmania) and bacterial (tuberculosis)and also autoimmune disease such as rheumatoid arthritis (RA). It has also been demonstrated that 5alpha-Dihydrotestosterone (5alpha-DHT) modulate nitric oxide and cytokine release by macrophages. These effects seem to be exerted by specific receptors for androgen in macrophages. MATERIAL/METHODS: Protein secretion: The effect of 5alpha-DHT on protein secretion by peritoneal macrophages of NZBBALBc mice was investigated using radiolabelled protein secretion following SDS-PAGE and Fluorography. Binding assay: Androgen binding was also investigated using an autoradiography method. Peritoneal macrophages were treated with [3H]- 5alpha-DHT and incubated for 2 h before smearing on to microscope slides. Slides were air dried, dipped in Kodak NTB photographic emulsion, sealed in light proof boxes and left at 4 degrees C for 6 weeks. RESULTS: The results showed that protein secretion by macrophages changed under 5alpha-DHT treatment. Analysis of the data according to quantitation of [(3)H]-5alphaDHT binding receptors in fixed-slide mounted cells, identified a high specific androgen binding at physiological concentration. The receptors had a relatively high affinity for the 5alpha-DHT, So that binding affinity was not inhibited in the presence of 100-fold excess of non labelled 17-beta Estradiol. CONCLUSIONS: These results suggest that the immunosuppressive action exerted by androgen is at least partially achieved through a direct influence on macrophages.