Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 16674108 | Activity-based matrix metallo-protease enrichment using automated, inhibitor affinity extr | 2006 May | An automated inhibitor affinity extraction method for the activity-based enrichment of matrix metallo-proteases (MMPs) is presented. Samples containing purified MMP-12 were first extracted at different flow rates in a syringe pump setup, using cartridges packed with an MMP inhibitor affinity sorbent based on an immobilized hydroxamic acid containing peptide (PLG-NHOH) with mumol/L MMP affinity. Faster extractions, a reduced number of manual manipulations, and higher extraction yields (98.9%-99.3%) were obtained over the whole flow rate range compared to batch extractions. Application of the method to synovial fluid from a rheumatoid arthritis patient followed by gelatin-zymography revealed a strong enrichment of distinct MMPs from this biological sample that were not clearly visible in the original sample. The use of an auto-sampler and a solid-phase extraction (SPE) workstation allowed full automation of the extraction procedure with the potential for on-line coupling to further sample preparation and analytical steps. MMP-12 extractions were optimized showing that ligand density is an important factor with a clear extraction yield optimum around 5 to 7.5 mmol/L. Conditioning of the stationary phase for 1 week prior to use resulted in a further slight increase in extraction yield. Under optimal conditions, an extraction yield of 99.5% was reached with a cartridge contact time of only 13 s for MMP-12. The efficacy of the extraction method for activity-based MMP profiling was further improved by the use of a broad-spectrum MMP inhibitor with nmol/L affinity (TAPI-2). This resulted in an increased extraction yield for all tested MMPs. For MMP-1, -7, -8, -10, -12, and -13 extraction yields of at least 98.8% were obtained, while for MMP-9 (full length and catalytic domain) an extraction yield of at least 96.1% was reached. | |
| 16514653 | Effect of wrist and ulna head position on gliding resistance of the extensor digitorum min | 2006 Apr | While attrition from sharp bony surfaces is the most common cause of extensor digiti minimi (EDM) tendon rupture, the etiology of other cases of spontaneous EDM tendon rupture is still unknown. Friction within the compartment may play a role, especially with ulna dislocation. The purpose of this study was to compare gliding resistance of the EDM tendon with that of a tendon which rarely ruptures spontaneously, the extensor digitorum communis of the middle finger (EDC III) tendon, under various wrist and ulna head positions. Eight fresh frozen cadavers were used. Gliding resistance between the tendon and its sheath in each compartment was measured in five different wrist positions and three different ulna head positions. Gliding resistance of the EDM tendon (0.13 +/- 0.03 N) was significantly greater than the EDC III tendon (0.09 +/- 0.03 N) (p < 0.05). For the EDM tendon, the gliding resistance in ulnar deviation or pronation was higher than the gliding resistance in neutral, radial deviation, or supination (p < 0.05), and the gliding resistance with ulnar lengthening (over 6 mm) or dorsal ulnar dislocation (over 9 mm) was higher than in neutral ulnar head positioning. For the EDC III tendon, the gliding resistance in ulnar deviation was significantly higher than the gliding resistance in neutral, radial deviation, or supination, or dorsal dislocation with ulnar lengthening (p < 0.05). Wrist ulnar deviation, ulnar dorsal dislocation (over 9 mm), and ulnar lengthening (over 6 mm) increased the gliding resistance of the EDM tendon. In patients at risk for EDM rupture, such as those with rheumatoid arthritis or distal radioulnar joint osteoarthritis, avoiding such positions may be advantageous. | |
| 16467190 | Celecoxib inhibits interleukin-12 alphabeta and beta2 folding and secretion by a novel COX | 2006 May | Celecoxib (CE) is a nonsteroidal anti-inflammatory drug (NSAID) that is a specific inhibitor of cyclooxygenase 2 (COX2). It is indicated for a variety of chronic inflammatory conditions, including rheumatoid arthritis. Over the last few years, adverse cardiovascular effects and increased risk for heart attacks have been associated with this drug. In addition, evidence is emerging for COX2-independent molecular targets. CE has been shown to induce apoptosis in various cancer cells lines through a COX2-independent mechanism that seems to involve inactivation of protein kinase Akt and inhibition of endoplasmic reticulum (ER) Ca2+ ATPase. In this study, we show that both CE and an analog devoid of COX2 inhibitory activity [1-(4-sulfamoyl phenyl)-3-trifluoromethyl-5-(4-trifluoromethylphenyl)pyrazole, CEA] inhibit the secretion of the dimeric interleukin-12 (IL-12) alphabeta and beta2 forms with identical IC50 values of 20 and 30 microM, respectively, whereas no such effect was seen with rofecoxib. Reverse transcription-polymerase chain reaction analysis showed that this inhibition was not due to a blockage of transcription of the alpha- and beta-chain expression cassettes. Secretion of the beta monomer form was less strongly inhibited, suggestive for a mechanism primarily targeting dimer assembly in the ER. Analysis of intracellular fractions revealed that both CE and CEA increased the association of IL-12 with calreticulin, an endoplasmic reticulum-resident chaperone involved in the retention of misfolded cargo proteins while blocking interaction with ERp44. Our findings reveal a previously undescribed effect of celecoxib on oligomer protein folding and assembly in the endoplasmic reticulum and ensuing secretion and suggest that celecoxib-driven alteration of the secretome may be involved in some of its clinical side effects. | |
| 16439062 | Remnant epitopes, autoimmunity and glycosylation. | 2006 Apr | The role of extracellular proteolysis in innate and adaptive immunity and the interplay between cytokines, chemokines and proteinases are gradually becoming recognized as critical factors in autoimmune processes. Many of the involved proteinases, including those of the plasminogen activator and matrix metalloproteinase cascades, and also several cytokines and chemokines, are glycoproteins. The stability, interactions with inhibitors or receptors, and activities of these molecules are fine-controlled by glycosylation. We studied gelatinase B or matrix metalloproteinase-9 (MMP-9) as a glycosylated enzyme involved in autoimmunity. In the joints of rheumatoid arthritis patients, CXC chemokines, such as interleukin-8/CXCL8, recruit and activate neutrophils to secrete prestored neutrophil collagenase/MMP-8 and gelatinase B/MMP-9. Gelatinase B potentiates interleukin-8 at least tenfold and thus enhances neutrophil and lymphocyte influxes to the joints. When cartilage collagen type II is cleaved at a unique site by one of several collagenases (MMP-1, MMP-8 or MMP-13), it becomes a substrate of gelatinase B. Human gelatinase B cleaves the resulting two large collagen fragments into at least 33 peptides of which two have been shown to be immunodominant, i.e., to elicit activation and proliferation of autoimmune T cells. One of these two remnant epitopes contains a glycan which is important for its immunoreactivity. In addition to the role of gelatinase B as a regulator in adaptive immune processes, we have also demonstrated that it destroys interferon-beta, a typical innate immunity effector molecule and therapeutic cytokine in multiple sclerosis. Furthermore, glycosylated interferon-beta, expressed in Chinese hamster ovary cells, was more resistant to this proteolysis than recombinant interferon-beta from bacteria. These data not only prove that glycosylation of proteins is mechanistically important in the pathogenesis of autoimmune diseases, but also show that targeting of glycosylated proteinases or the use of glycosylated cytokines seems also critical for the treatment of autoimmune diseases. | |
| 16321451 | Behavior, neurocognition and quality-of-life in children with sleep-disordered breathing. | 2006 Mar | OBJECTIVES: To summarize current evidence that sleep-disordered breathing in children is associated with behavioral, neurocognitive and quality-of-life problems and to suggest new lines of investigation for future research on sleep-disordered breathing and behavior. METHODS: A comprehensive review of the medical literature between January 1990 and December 2004 was performed using the National Library of Medicine's PUBMED database. RESULTS: Analysis revealed 33 articles that satisfied the inclusion and exclusion criteria. The total study population in these articles was 22,255 children. Sample sizes per study ranged from 12 to 5728 children. The age range was 2-18 years (mean 6.8+/-2.8). The majority of studies examined behavior, neurocognition or quality-of-life as a single outcome measure. Behavioral problems included reduced attention, hyperactivity, increased aggression, irritability, emotional and peer problems, and somatic complaints. The following neurocognitive skills were affected: memory; immediate recall; visual-spatial functions; attention and vigilance; mental flexibility; and intelligence. The quality-of-life of children with sleep-disordered breathing was similar that of children with asthma or rheumatoid arthritis. Improvements in behavior, neurocognition and quality-of-life scores for children with sleep-disordered breathing were seen after adenotonsillectomy. CONCLUSIONS: There is compelling evidence that sleep-disordered breathing in children is associated with behavioral and neurocognitive problems and leads to reduced quality-of-life. In addition to improvements in sleep, adenotonsillectomy is associated with improvements in behavior, neurocognition and quality-of-life in these children. However, the lack of uniform criteria for the diagnosis of sleep-disordered breathing in children and variation in methods used to assess the outcome of surgical therapy limit our current knowledge and should be addressed by future research. The high prevalence of sleep-disordered breathing in children should make this research a public health priority. | |
| 16049983 | Personal and family history of autoimmune diabetes mellitus and susceptibility to young-ad | 2006 Jan 15 | Young-adult-onset (15-44 years of age) Hodgkin lymphoma (HL) is believed to arise as a consequence of late primary infection in susceptible individuals. The properties of this susceptibility remain little understood. We have previously reported an increased occurrence of HL in patients with rheumatoid arthritis and among their offspring, suggesting that susceptibility to autoimmunity might be of importance also in the pathogenesis of HL. To explore this hypothesis, we assessed the association of personal and family history of diabetes mellitus, with risk of subsequent HL in a population-based case-control study, including as cases all individuals diagnosed with HL above 15 years of age 1964-1999 (n = 6,873) in Sweden, and matched population controls (n = 12,565). First-degree relatives of cases and controls were identified through linkage with the Multi-generation Register. We identified discharges listing diabetes mellitus through linkage with the Inpatient Register (1964-2000). We used odds ratios (OR) as measures of relative risk. Cases with young-adult-onset HL were less likely to have a personal (OR =0.5, 95% CI 0.2-1.1) or family (OR =0.7, 95% CI 0.6-0.8) history of diabetes mellitus. In contrast, HL diagnosed at older ages was neither associated with a personal (OR =1.0) nor family (OR =1.0) history of diabetes mellitus. These findings suggests that characteristics of the immune system associated with conditions such as diabetes mellitus type I are of importance in the pathogenesis of young-adult-onset HL. | |
| 19086827 | Does vitamin D make the world go 'round'? | 2008 Dec | Abstract Vitamin D has emerged from obscurity, and its effects on various organ systems throughout the body down to the cellular level are being discovered. What was once thought to be a simple hormone affecting only bone and calcium metabolism has shifted. We no longer see vitamin D as a "vitamin" important only in childhood, but as a complex hormone that is involved not only in calcium homeostasis but also in the integrity of the innate immune system. Vitamin D deficiency is linked to inflammatory and long-latency diseases such as multiple sclerosis, rheumatoid arthritis, tuberculosis, diabetes, and various cancers, to name a few. In this review, we trace how we came to view vitamin D and how that view led to one of the largest epidemics of nutrient deficiency beginning in the late 20(th) century. We then discuss the needs of vitamin D in the context of the breastfeeding mother and her infant and child, why breastfed infants are particularly at risk, and what to do about it. | |
| 16715948 | Comparison of extraarticular leakage values of radiopharmaceuticals used for radionuclide | 2006 Apr | OBJECTIVES: Radionuclide synovectomy is a reliable therapy in patients with chronic synovitis. However, radiation doses delivered to non-target organ systems due to leakage of radioactive material from the articular cavity are an important disadvantage of this procedure. In this study we compared extraarticular leakage values of the 3 commonly used radiopharmaceuticals; 90Y-citrate, 90Y-silicate and 186Re-sulfide colloid. MATERIALS AND METHODS: Thirty-five patients with persistent synovitis were enrolled in the study. Twenty-two hemophilic, 8 rheumatoid arthritis and 5 patients with pigmented villonodular synovitis were studied. 90Y labeled silicate and citrate were used for knee joints and 186Re-sulfide for intermediate sized joints. Radiocolloid leakage values were evaluated using a gamma camera with 20% window centered over the bremsstrahlung photopeak of 90Y and a respective window over the 137 keV photopeak of 186Re. Regions of interest were drawn over the injection site, the regional lymph nodes and the background areas. Leakage of radiocolloid was calculated by dividing the counts/pixel in the regional lymph node area to the counts/pixel in the injection site. RESULTS: No visible leakage was observed. The median leakage values calculated for 90Y-citrate, 90Y-silicate and 186Re-sulfide were found as 1.9%, 2.4% and 2.7%, respectively. The difference between the variability of leakage values was not statistically significant (p > 0.05). CONCLUSION: There was no significant difference in terms of extraarticular leakage between 9Y-citrate, 9Y-silicate and 186Re-sulfide radiocolloids. | |
| 16652151 | Stromelysin-1 expression is activated in vivo by Ets-1 through palindromic head-to-head Et | 2006 Sep 21 | Regulation of the gene expression of Stromelysin-1 (matrix metalloproteinase-3), a member of the matrix metalloproteinase family, is critical for tissue homeostasis. The Stromelysin-1 promoter is known to be transactivated by Ets proteins through palindromic head-to-head Ets binding sites (EBS), an unusual configuration among metalloproteinase promoters. Patterns of increased co-expression of Stromelysin-1 and Ets-1 genes have been observed in pathological processes such as rheumatoid arthritis, glomerulonephritis and tumor invasion. In this context, we show in a synovial fibroblastic model cell line (HIG-82), which is able to co-express Stromelysin-1 and Ets-1, that the EBS palindrome is essential for the expression of Stromelysin-1. More precisely, using electrophoretic mobility shift assays, DNA affinity purification and chromatin immunoprecipitation, we demonstrate that endogenous Ets-1, but not Ets-2, is present on this palindrome. The use of a dominant-negative form of Ets-1 and the decrease of Ets-1 amount either by fumagillin, an antiangiogenic compound, or by short interfering RNA show that the activation rate of the promoter and the expression of Stromelysin-1 correlate with the level of endogenous Ets-1. Thus, it is the first demonstration, using this cellular model, that endogenously expressed Ets-1 is actually a main activator of the Stromelysin-1 promoter through its effective binding to the EBS palindrome. | |
| 16626851 | The rational designed antagonist derived from the complex structure of interleukin-6 and i | 2006 Sep | Human interleukin-6 is involved in the maintenance and progression of several diseases such as multiple myeloma (MM), rheumatoid arthritis, or osteoporosis. Our previous work demonstrated that an interleukin-6 antagonist peptide (named PT) possessed potential bioactivity to antagonize the function of hIL-6 and could efficiently induce the growth arrest and apoptosis of XG-7 and M1 cells in a dose-dependent manner. In this study, the theoretical interaction of the peptide PT with its receptor was analyzed further more with molecular docking and molecular dynamics methods. The theoretical studies showed that PT possessed very high affinity to interleukin-6R and offered a practical means of imposing long-term blockade of interleukin-6 activity in vivo. According to the theoretical results, the biological evaluation of PT was researched on two different cells models with more sensitive approaches: (1) The antagonist activity of PT was studied on the interleukin-6 dependent MM cells (XG-7) cultured with interleukin-6. In the other interleukin-6 dependent MM cells (SKO-007), they survived themselves by auto/paracrine without the exogenous interleukin-6, and also could be antagonized by PT. The therapeutic value of PT only limited on the interleukin-6 dependent category in MM. (2) Myeloid leukemia M1 cells were induced for growth arrest and apoptosis in response to interleukin-6. The results supported our previous findings and showed that PT could be evaluated by protecting the cells from interleukin-6 induced apoptosis. In conclusion, PT could induce interleukin-6-dependent XG-7 and SKO-007 cells to apoptosis while inhibit interleukin-6-stimulated apoptosis in M1 cells. | |
| 18796047 | Transition to adult care: experiences and expectations of adolescents with a chronic illne | 2008 Sep | BACKGROUND: Effective means of transitioning adolescent patients with chronic illness from paediatric to adult medical care are poorly documented and supported by limited evidence. The purpose of this study is to describe expectations and concerns of adolescents with chronic illness regarding transition from subspecialty paediatric to adult-centred care during the transition process in order guide effective programme design and implementation. METHODS: Qualitative content and thematic analysis of semi-structured individual interviews with 22 adolescents with chronic illness, including cystic fibrosis, sickle cell disease, juvenile rheumatoid arthritis, and inflammatory bowel disease. Interviews took place at 1-3 time points over an 18-month study period. RESULTS: Transition topics included: timing of transfer to adult care, the transition process, attitudes about transition, and factors that might aid transition. During the study period, one-third of participants made the transition to adult-oriented health care. All participants who had transitioned to adult-oriented care reported participating in a structured transition programme. Concerns of those who had not initiated the transition process centred on re-establishing relationships and bringing a new team 'up to speed'. Most adolescents anticipating transfer to adult care identified only downsides and felt unprepared to transition at the time of the interview. Subjects who had transitioned noted benefits of the adult-oriented system, even if they had been ambivalent prior to transfer of care. Participants suggested that earlier discussions about transition, opportunities to meet new healthcare teams and visits to adult-oriented venues prior to transition might aid in the transition process. CONCLUSIONS: Subspecialty paediatric providers should anticipate common fears and concerns of adolescents and discuss the benefits of transfer to adult-oriented care. Further evaluation of existing transition programmes is an area for future study and is necessary for improvement of the continuum of care for adolescents with chronic medical conditions. | |
| 18726597 | Interstitial lung disease associated with collagen vascular disorders: disease quantificat | 2009 Feb | The purpose of this study was to evaluate a computer-aided diagnosis (CAD) tool compared to human observers in quantification of interstitial lung disease (ILD) in patients with collagen-vascular disorders. A total of 52 patients with rheumatoid arthritis (n=24), scleroderma (n=14) and systemic lupus erythematosus (n=14) underwent thin-section CT. Two independent observers assessed the extent of ILD (EoILD), reticulation (EoRet) and ground-glass opacity (EoGGO). CAD assessed EoILD twice. Pulmonary function tests were obtained. Statistical evaluation used 95% limits of agreement and linear regression analysis. CAD correlated well with diffusing capacity (DL(CO)) (R= -0.531, P<0.0001) and moderately with forced vital capacity (FVC) (R= -0.483, P=0.0008). There was close correlation between CAD and the readers (EoILD vs. CAD: R=0.716, P<0.0001; EoRet vs. CAD: R=0.69, P<0.0001). Subgroup analysis including patients with minimal EoGGO (<15%) strengthened the correlations between CAD and the readers, readers and PFT, and CAD and PFT. EoILD by readers correlated strongly with DL(CO) (R= -0.705, P<0.0001) and moderately with FVC (R= -0.559, P=0.0002). EoRet correlated closely with DL(CO) and moderately with FVC (DL(CO): R= -0.663; FVC: R = -0.436; P | |
| 18700910 | Inflammation in atherosclerosis and psoriasis: common pathogenic mechanisms and the potent | 2008 Aug | Inflammation plays a key role in the pathogenesis of a number of chronic inflammatory systemic diseases (CISDs), including psoriasis, rheumatoid arthritis, systemic lupus erythematosus and Crohn's disease, and also in the pathogenesis of atherosclerosis. CISDs and cardiovascular diseases, such as atherosclerosis, share common pathogenic features, and cardiovascular disease is an important cause of morbidity and mortality in patients with CISDs. Activated inflammatory cells and pro-inflammatory cytokines contribute to the development of psoriatic lesions and play an important role in the breakdown of atherosclerotic plaques. Psoriasis and atherosclerosis also have similar histological characteristics involving T cells, macrophages and monocytes. In particular, the extravasation of T cells through the epithelium is characteristic of both psoriatic and atherosclerotic plaques. Cardiovascular disease is an important cause of morbidity and mortality in patients with psoriasis, which is associated with an increased cardiovascular risk profile compared with the general population. Patients with psoriasis are at increased risk of arterial hypertension, coronary heart disease, hyperlipidaemia, obesity and type II diabetes, which are more prevalent than in control patients. This increased risk could be due to the effects of chronic inflammatory changes, particularly the infiltration of T cells and subsequent secretion of pro-inflammatory cytokines. Some drugs used in the treatment of cardiovascular disease, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors have anti-inflammatory activity. In addition, systemic treatments for psoriasis may, by decreasing inflammation, reduce the risk of cardiovascular disease. It is suggested, therefore, that an integrated approach to the treatment of the inflammatory processes underlying both psoriasis and atherosclerosis may be beneficial in reducing cardiovascular risk in patients with psoriasis. The newer targeted biological therapies, such as efalizumab and infliximab, which offer the potential for long-term disease control in psoriasis, may be of particular use in this setting. | |
| 18703007 | B cells and multiple sclerosis. | 2008 Sep | Clonal expansion of B cells and the production of oligoclonal IgG in the brain and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) have long been interpreted as circumstantial evidence of the immune-mediated pathogenesis of the disease and suggest a possible infectious cause. Extensive work on intrathecally produced antibodies has not yet clarified whether they are pathogenetically relevant. Irrespective of antibody specificity, however, the processes of antibody synthesis in the CNS of patients with MS are becoming increasingly clear. Likewise, targeting B cells might be therapeutically relevant in MS and other autoimmune diseases that are deemed to be driven predominantly by T cells. Accumulating evidence indicates that in MS, similar to rheumatoid arthritis, B cells aggregate into lymphoid-like structures in the target organ. The process of aggregation is mediated through the expression of lymphoid-homing chemokines. In the brain of a patient with MS, ectopic B-cell follicles preferentially adjoin the pial membrane within the subarachnoid space. Recent findings indicate that substantial numbers of B cells that are infected with Epstein-Barr virus (EBV) accumulate in these intrameningeal follicles and in white matter lesions and are probably the target of a cytotoxic immune response. These findings, which await confirmation, could be an explanation for the continuous B-cell and T-cell activation in MS, but leave open concerns about the possible pathogenicity of autoantibodies. Going beyond the antimyelin-antibody dogma, the above data warrant further work on various B-cell-related mechanisms, including investigation of B-cell effector and regulatory functions, definition of the consistency of CNS colonisation by Epstein-Barr virus-infected B cells, and understanding of the mechanisms that underlie the formation and persistence of tertiary lymphoid tissues in patients with MS and other chronic autoimmune diseases (ectopic follicle syndromes). This work will stimulate new and unconventional ways of reasoning about MS pathogenesis. | |
| 18695259 | Osteonecrosis of the maxilla and mandible in patients with advanced cancer treated with bi | 2008 Aug | Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past 5 years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate (IVBP) therapy, but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. To further categorize risk factors associated with ONJ and potential clinical outcomes of this condition, we performed a retrospective study of patients with metastatic bone disease treated with intravenous bisphosphonates who have been evaluated by the Memorial Sloan-Kettering Cancer Center Dental Service between January 1, 1996 and January 31, 2006. We identified 310 patients who met these criteria. Twenty-eight patients were identified as having ONJ at presentation to the Dental Service and an additional 7 patients were subsequently diagnosed with ONJ. Statistically significant factors associated with increased likelihood of ONJ included type of cancer, duration of bisphosphonate therapy, sequential IVBP treatment with pamidronate followed by zoledronic acid, comorbid osteoarthritis or rheumatoid arthritis, and benign hematologic conditions. Our data do not support corticosteroid use or oral health as a predictor of risk for ONJ. Clinical outcomes of patients with ONJ were variable with 11 patients demonstrating improvement or healing with conservative management. Our ONJ experience is presented here. | |
| 18694811 | Stability and bioactivity of nanocomplex of TNF-related apoptosis-inducing ligand. | 2008 Nov 3 | The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has gained much attention due to its potent therapeutic effect for cancer and rheumatoid arthritis. In this study, we attempted to develop the injectable formulations which can stabilize TRAIL and thus show prolonged blood circulation in vivo. The positively charged TRAIL was mixed with hyaluronic acid (HA), resulting in the formation of nanocomplexes. The zeta-potentials of nanocomplexes and their mean diameters were significantly dependent on the feed ratio of HA to TRAIL. The increase in the feed ratio of HA reduced the particle size and decreased the value of the zeta-potential. The bioactivity of TRAIL in the complexes was comparable to that of native TRAIL, indicating that the complex formation did not affect the activity of TRAIL. Furthermore, the stability of TRAIL in the complexes was retained for 6 days, during which the bioactivity of native TRAIL disappeared. When native TRAIL was subcutaneously injected into the rats, its plasma concentration was not detectable after 12h. In contrast, for HA/TRAIL nanocomplexes in 1% HA solution, substantial amount of TRAIL was circulated in blood for up to 5 days. These results imply that HA-based formulations of TRAIL hold the potential as the therapeutics. | |
| 18510238 | [Vitrectomy in vitreo-retinal complications associated with intermediate uveitis]. | 2008 Jan | OBJECTIVE: To investigate the effects of vitrectomy in vitreo-retinal complications associated with intermediate uveitis. METHODS: Retrospective case series of sixteen eyes of 16 patients in vitreo-retinal disease associated with intermediate uveitis in a 3-year period from Mar 2002 to Jun 2005 were included in the study. They were treated with vitrectomy and the mean follow-up was (14.25 +/- 7.90) months (range: 5-32 months). Visual acuity in final follow-up, post-operative complications and the recurrence of intermediate uveitis were retrospectively reviewed. RESULTS: Four patients were associated with tuberculosis, rheumatoid arthritis, multiple sclerosis or Behcet disease, respectively. The remaining 12 cases had idiopathic diseases. Pre-operatively, all patients were treated with steroids for a long time and the mean treatment time was (9.94 +/- 2.67) months (range: 6-16 months). Pre-operative vitreo-retinal complications included severe vitreous organization (5 eyes), tractional retinal detachment (6 eyes), rhegmatogenous retinal detachment (1 eye), vitreous hemorrhages (2 eyes), epimacular membrane (2 eyes) accompanied with vitreous tissue, and peripheral retinal neovascularization (16 eyes). In the post-operative period, tractional retinal detachment in one eye and complicated cataract in 3 eyes were observed. Post-operatively, only 4 cases need long-term immunosuppression therapy (more than 6 months). Fourteen of 16 eyes achieved a final visual acuity equal to or better than baseline (X2 = 4.923, P < 0.05). Recurrent intermediate uveitis was not found in these patients. CONCLUSIONS: The results of this study suggest that pars plana vitrectomy may have a beneficial effect on the intermediate uveitis which was severe or uncontrolled by immunosuppressive drugs and accompanied with vitreo-retinal complications. The beneficial effects include improving visual acuity, reducing need for long-term immunosuppression treatment. | |
| 18296349 | Anti-angiogenic function of tocotrienol. | 2008 | Angiogenesis means the formation of new blood vessels from preexisting vascular, is of fundamental importance in several pathological states such as tumor growth, rheumatoid arthritis, and diabetic retinopathy. Angiogenesis involves a set of steps, including activation and movement of endothelial cells and tube formation. Control of these steps by drugs or dietary food components is a hopeful approach for the prevention of angiogenic disorders. Based on these backgrounds, we searched the anti-angiogenic food components. As a result, we found that tocotrienol (T3), especially delta, beta, and gamma-T3 has the potent anti-angiogenic activity in vitro and in vivo experiments. T3, which is rich in rice bran and palm oil, inhibited growth factor-induced proliferation, migration and tube formation in human umbilical vein endothelial cells. T3 showed inhibition of tumor cell-induced angiogenesis in mouse dorsal air sac (DOS) assay. These results indicated that T3 is a potent anti-angiogenesis compound. Tocopherol (Toc) did not inhibit angiogenesis. The anti-angiogenic mechanism of T3 and Toc was evaluated by western blotting. T3 inhibited activation of growth factor-induced extracellular signal-regulated kinase, Akt (protein kinase B), and endothelial nitric oxide synthase (eNOS), which are located downstream of the various growth factor receptors. T3 suppressed phosphorylation of vascular endothelial growth factor (VEGF) receptor 2. These effects were dose-dependent manner. Anti-angiogenic mechanism of T3 mediates inhibition of growth factor induced survival, migration and angiogenesis signals. These findings suggested that T3 may have potential for preventing angiogenic disorders in humans. | |
| 18464299 | WHO-ILAR COPCORD Study (Stage 1, Urban Study) in Iran. | 2008 Jul | OBJECTIVE: To find the prevalence of musculoskeletal complaints and rheumatic disorders in Iran. METHODS: Tehran, with one-ninth of the population of Iran and of mixed ethnic origins, was selected as the field. Subjects were randomly selected from the 22 districts. Interviews were conducted once a week, on the weekend. The 3 phases of stage 1 were done on the same day, in parallel, like the fast-track Community Oriented Program for Control of Rheumatic Diseases (COPCORD). RESULTS: Four thousand ninety-six houses were visited and 10,291 persons were interviewed. Musculoskeletal complaints during the past 7 days were detected in 41.9% of the interviewed subjects. The distribution was: shoulder 14.5%, wrist 10%, hands and fingers 9.4%, hip 7.1%, knee 25.5%, ankle 9.8%, toes 6.1%, cervical spine 13.4%, and dorsal and lumbar spine 21.7%. Degenerative joint diseases were detected in 16.6% of subjects: cervical spondylosis 1.8%, knee osteoarthritis (OA) 15.3%, hand OA 2.9%, and hip OA 0.32%. Low back pain was detected in 15.4% and soft tissue rheumatism in 4.6%. Inflammatory disorders were rheumatoid arthritis 0.33%, seronegative spondyloarthropathies 0.23%, ankylosing spondylitis 0.12%, systemic lupus erythematosus 0.04%, and Behçet's disease 0.08%. Fibromyalgia was detected in 0.69% and gout in 0.13% of the studied population. CONCLUSION: The large urban COPCORD study in Iran showed a high prevalence of rheumatic complaints in the population over the age of 15 years, 41.9%. Knee OA and low back pain were the most frequent complaints. | |
| 18445626 | Infliximab efficacy and safety against refractory systemic necrotising vasculitides: long- | 2008 Sep | BACKGROUND: Results of uncontrolled studies have suggested that infliximab is efficacious against systemic necrotising vasculitides (SNV) refractory to conventional treatment. However, its safety and ability to induce and maintain remission over the long term remain unknown. OBJECTIVES: To report the use of infliximab to treat refractory SNV, focusing on patients' longer-term outcomes. METHODS: The medical charts of patients given adjunctive infliximab for refractory SNV >/=2 years before this evaluation were reviewed retrospectively. RESULTS: The 15 patients (median age 46 (range 20-69) years, median follow-up 35 (24-41) months) included 10 with Wegener's granulomatosis, 1 microscopic polyangiitis, 3 rheumatoid arthritis-associated and 1 cryoglobulinaemia-related vasculitides. Infliximab was taken for a median time of 8 (2-31) months; 2 patients are still being treated. By day 45, 11 patients had entered remission (Birmingham Vasculitis Activity Score (BVAS) = 0) and 4 others had responded (BVAS decrease >/=50%). Five patients achieved sustained remissions (>/=6 months, corticosteroids |