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ID PMID Title PublicationDate abstract
22786533 Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene trans 2013 Apr Antibodies against adeno-associated viral (AAV) vectors are highly prevalent in humans. Both preclinical and clinical studies showed that antibodies against AAV block transduction even at low titers, particularly when the vector is introduced into the bloodstream. Here we measured the neutralizing antibody (NAb) titer against AAV serotypes 2, 5, 6 and 8 in the serum and matched synovial fluid (SF) from rheumatoid arthritis patients. The titer in the SF was lower than that in the matched plasma samples, indicating a difference in distribution of NAb to AAV depending on the body fluid compartment. This difference was more evident for AAV2, against which higher titers were measured. Of all serotypes, anti-AAV5 antibodies were the least prevalent in both the serum and SF. We next evaluated the impact of B-cell depletion on anti-AAV antibodies in rheumatoid arthritis patients who received one or two courses of the anti-CD20 antibody rituximab as part of their disease management. A drop of NAb titer was observed in a subset of those subjects carrying NAb titers ≤1:1000; however, only in a minority of subjects titers dropped below 1:5. This work provides insights into strategies to overcome the limitation of pre-existing humoral immunity to AAV vectors.
21600098 [Modulation of RhoA/ROCK pathway on TLR-2 ligand-induced chemokine secretion in fibroblast 2011 Mar 22 OBJECTIVE: To evaluate the modulation of RhoA/Rho kinase (ROCK) signaling pathway, a small Rho GTPase that is considered as an important modulator in inflammatory responses, on Toll-like receptor-2 mediated chemokine secretion in fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. METHODS: The RhoA activity was measured by a pull-down assay. And the ROCK activity was assessed by Western blot. The secretion of chemokines was measured by ELISA (enzyme-linked immunosorbent assay). MTT test was used to detect the cellular viability. RESULTS: The stimulation of peptidoglycan (PG, 5 mg/L) increased the levels of IL-8 (interleukin-8), RANTES (regulated upon activation normal T cell expressed & secreted) and MCP-2 (monocyte chemotactic protein-2) and boosted the activities of RhoA and ROCK versus the unstimulated RA FLS. And these effects of PG were suppressed by anti-TLR-2 monoclonal antibody. Inhibition of RhoA and ROCK with a specific inhibitor inhibited the secretion of IL-8, RANTES and MCP-2 in PG-induced RA FLS. CONCLUSION: The present study provides novel evidence that the RhoA/ROCK signal pathway modulates the TLR-2-mediated secretion of chemokines in RA FLS. It suggests that the inhibition of RhoA/ROCK may be a new therapeutic approach for RA.
22739990 Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate 2013 Jun OBJECTIVE: To investigate the long-term effects of induction therapy with adalimumab (ADA) plus methotrexate (MTX) in comparison with placebo (PBO) plus MTX in DMARD-naïve patients with active early rheumatoid arthritis (RA). METHODS: Patients with active early RA (disease duration of ≤12 months) were randomly assigned to receive 40 mg ADA subcutaneously every other week (eow) plus MTX 15 mg/week subcutaneously or PBO plus MTX subcutaneously at 15 mg/week over 24 weeks. Thereafter, all patients received MTX monotherapy up to week 48. The primary outcome was the Disease Activity Score 28 (DAS28) at week 48. Secondary outcomes included proportions of patients in remission (DAS28<2.6), ACR responses, Health Assessment Questionnaire (HAQ) score and radiographic progression. RESULTS: 87 patients were assigned to ADA/MTX and 85 patients to PBO/MTX. At baseline, DAS28 was 6.2±0.8 in the ADA/MTX and 6.3±0.9 in the PBO/MTX groups. At week 24, treatment with ADA/MTX compared with PBO/MTX resulted in a greater reduction in DAS28 (3.0±1.2 vs 3.6±1.4; p=0.009) and other secondary outcomes such as DAS28 remission rate (47.9% vs 29.5%; p=0.021) and HAQ (0.49±0.6 vs 0.72±0.6; p=0.0014). At week 48, the difference in clinical outcomes between groups was not statistically significant (DAS28: 3.2±1.4 vs 3.4±1.6; p=0.41). Radiographic progression at week 48 was significantly greater in patients administered PBO/MTX (Sharp/van der Heijde score: ADA/MTX 2.6 vs PBO/MTX 6.4; p=0.03, Ratingen score: 1.7 vs 4.2; p=0.01). CONCLUSIONS: A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48, even after discontinuation of ADA treatment at week 24. This sustained effect was not found at the primary endpoint (DAS28 reduction).
22467934 YouTube for information on rheumatoid arthritis--a wakeup call? 2012 May OBJECTIVE: Rheumatoid arthritis (RA) is a common debilitating autoimmune disease, with unmet need for knowledge among patients and the general population. YouTube is a popular, consumer-generated, video-sharing website, which can be a source of information on RA. We investigated the quality of information on RA on YouTube and analyzed audience interaction. METHODS: YouTube was searched using the term "Rheumatoid Arthritis," for videos uploaded on RA. Two physicians independently classified videos as useful, misleading, or patient views, and rated them on a 5-point global quality scale (GQS; 1 = poor quality, 5 = excellent quality). Useful videos were rated for reliability and content, on a 5-point scale (higher scores represent more reliable and comprehensive videos). Source of videos was also noted. Audience interaction was assessed through video viewership. RESULTS: A total of 102 relevant videos were identified; 54.9% were classified as useful (GQS 2.9 ± 1.0) and 30.4% deemed misleading (GQS 1.3 ± 1.6). Mean reliability and content score of useful videos was 3.2 (± 1.0) and 2.5 (± 1.2), respectively. All videos uploaded by university channels and professional organizations provided useful information but formed only 12.7% of total videos, whereas 73.9% of medical advertisements and videos by for-profit organizations were misleading. There was no difference in the viewership/day (10.0 vs 21.5; p = nonsignificant) of useful and misleading information. CONCLUSION: YouTube is a source of information on RA, of variable quality, with wide viewership and potential to influence patients' knowledge and behavior. Physicians and professional organizations should be aware of and embrace this evolving technology to raise awareness about RA, and empower patients to discriminate useful from misleading information.
22414301 Chondrogenic differentiation of human subchondral progenitor cells is affected by synovial 2012 Mar 13 BACKGROUND: Microfracture is a first-line treatment option for cartilage repair. In microfracture, subchondral mesenchymal cortico-spongious progenitor cells (CSP) enter the defect and form cartilage repair tissue. The aim of our study was to investigate the effects of joint disease conditions on the in vitro chondrogenesis of human CSP. METHODS: CSP were harvested from the subchondral bone marrow. CSP characterization was performed by analysis of cell surface antigen pattern and by assessing the chondrogenic, osteogenic and adipogenic differentiation potential, histologically. To assess the effect of synovial fluid (SF) on chondrogenesis of CSP, micro-masses were stimulated with SF from healthy (ND), osteoarthritis (OA) and rheumatoid arthritis donors (RA) without transforming growth factor beta 3. RESULTS: CSP showed the typical cell surface antigen pattern known from mesenchymal stem cells and were capable of osteogenic, adipogenic and chondrogenic differentiation. In micro-masses stimulated with SF, histological staining as well as gene expression analysis of typical chondrogenic marker genes showed that SF from ND and OA induced the chondrogenic marker genes aggrecan, types II and IX collagen, cartilage oligomeric matrix protein (COMP) and link protein, compared to controls not treated with SF. In contrast, the supplementation with SF from RA donors decreased the expression of aggrecan, type II collagen, COMP and link protein, compared to CSP treated with SF from ND or OA. CONCLUSION: These results suggest that in RA, SF may impair cartilage repair by subchondral mesenchymal progenitor cells in microfracture, while in OA, SF may has no negative, but a delaying effect on the cartilage matrix formation.
22266038 Balancing hERG affinity and absorption in the discovery of AZD5672, an orally active CCR5 2012 Feb 15 Modifications to a series of potent and selective substituted 1-(3,3-diphenylpropyl)-piperidine phenylacetamide CCR5 antagonists were explored with the aim of reducing affinity at the hERG cardiac ion channel. Replacement of one aromatic ring in the diphenylpropyl region with less lipophilic, saturated heterocyclic rings and subsequent optimisation of the other phenyl ring led to the identification of clinical compound AZD5672 which retained excellent potency while reducing hERG affinity. Modulating lipophilicity affected the interplay between potency, hERG affinity and absorption. AZD5672 was found to have an acceptable balance of these properties and was progressed to a phase II clinical trial to test the hypothesis that inhibition of CCR5 will bring benefits in the treatment of rheumatoid arthritis.
22798682 Enhanced Th17 differentiation and aggravated arthritis in IEX-1-deficient mice by mitochon 2012 Aug 15 CD4(+) Th1 and Th17 cells both can cause autoimmune diseases, either alone or collaboratively, if left unchecked. However, what determines the dominant Th effector phenotype in a specific autoimmune disease remains poorly understood. Our present investigation shows that null mutation of IEX-1 promotes differentiation of Th17 cells but compromises the survival of Th1 cells. The differential effect gave rise to a greater number of Th17 cells, a higher level of IL-17 production, and more severe arthritis in IEX-1 knockout mice than in wild-type mice after immunizations with collagen. IEX-1 deficiency-facilitated Th17 cell differentiation was mediated by the increased formation of reactive oxygen species (ROS) at mitochondria following T cell activation, as suggested by marked inhibition of Th17 induction with ROS scavenger N-acetylcysteine or mitoquinone, a specific inhibitor for mitochondrial ROS production. Mitochondrial ROS augmented the expression of B cell-activating transcription factor, which may contribute to increased IL-17 production in the absence of IEX-1, in light of its importance in IL-17 transcription. The results demonstrate that mitochondrial ROS contribute significantly to the dominant Th effector phenotype in autoimmunity in addition to the cytokine milieu.
23223421 Toll-like receptor-mediated, enhanced production of profibrotic TIMP-1 in monocytes from p 2013 Aug OBJECTIVES: To investigate whether monocytes contribute to matrix deposition in systemic sclerosis (SSc) by production of tissue-inhibitor of metalloproteinase-1 (TIMP-1). METHODS: Matrix metalloproteinase-1 (MMP-1) and TIMP-1 expression and secretion were measured by qRT-PCR and ELISA in circulating monocytes from patients with SSc, patients with rheumatoid arthritis (RA) and healthy controls (HC) and in healthy monocytes cultured in the presence of SSc or HC serum samples. Production of TIMP-1 was determined in response to a panel of Toll-like receptor (TLR) agonists and MyD88 inhibitory peptide. The functional effect of conditioned media from SSc and HC serum samples or TLR8-stimulated monocytes was studied in an MMP-1 activity assay. RESULTS: TIMP-1 production by monocytes was upregulated in patients with SSc compared with patients with RA and HC. Incubation of HC monocytes with SSc serum samples resulted in functionally active TIMP-1 production. However, pretreatment with MyD88 inhibitor, but not control peptide, decreased TIMP-1 secretion. TIMP-1 production was significantly stronger when SSc and HC monocytes were stimulated with TLR8 (ssRNA) agonist, but the response was more pronounced in SSc monocytes. TIMP-1 production after TLR stimulation was also strongly reduced in the presence of MyD88 inhibitory peptide or in the monocytes isolated from a patient with a genetic TLR signalling defect. MMP-1 activity was significantly inhibited in media from serum samples or TLR8-stimulated monocytes indicative of functional TIMP activity. CONCLUSIONS: This study demonstrates profibrotic properties of circulating monocytes from patients with SSc and a key role for TLR signalling, particularly TLR8, in TIMP-1 secretion and matrix remodelling.
21125300 Endoscopic transnasal resection of the odontoid: case series and clinical course. 2011 Apr The transoral route is the gold standard for odontoid resection. Results are satisfying though surgery can be challenging for patients and surgeons due to its invasiveness. A less invasive transnasal approach could provide a sufficient extent of resection with less collateral damage. The technique of transnasal endoscopic odontoid resection is demonstrated by a case series of three patients. A fully endoscopic transnasal odontoid resection was conducted by use of CT-based neuronavigation. A complete odontoid resection succeeded in all patients. Symptoms such as dysarthria, swallowing disturbance, salivary retention, myelopathic gait disturbances, neck pain, and tetraparesis improved in all patients markedly. Transnasal endoscopic odontoid resection is a feasible alternative to the transoral technique. It leaves the oropharynx intact, which could result in lower approach related complications especially in patients with bulbar symptoms.
21778031 Results of a second-generation constrained condylar prosthesis in primary total knee arthr 2011 Dec This is a prospective study of the results of a second-generation modular constrained condylar knee (CCK) prosthesis in primary total knee arthroplasty. Of 418 consecutive total knee arthroplasties performed by 1 surgeon, a second-generation modular CCK prosthesis was indicated for intraoperative stability in 30 knees (7.2%). Three knees were lost to follow-up, and 27 knees had a mean follow-up time of 5.4 years (range, 2-11.5 years). All tibial components had a cemented 35-mm stem extension, and 26 femoral components had a 100-mm uncemented stem extension. The indication for use of the CCK components was most commonly severe valgus deformity and incompetent medial collateral ligament. There were no revisions for loosening, patella problems, or tibial post fracture. A lateral retinacular release of the patella was performed in 6 knees (22%). An asymptomatic, minimally displaced patella fracture was noted in 2 knees (7.4%). Constrained condylar knees are used infrequently now but are successful for the treatment of the unstable primary knee that cannot be balanced. These results may be design specific.
23263277 Role of FK506 binding protein 5 (FKBP5) in osteoclast differentiation. 2013 Nov OBJECTIVES: We previously disclosed the enhanced expression of FK506 binding protein 5 (FKBP5) messenger RNA (mRNA) in bone marrow (BM) CD34(+) cells in rheumatoid arthritis (RA), in which systemic osteoporosis takes place. Since BM CD34(+) cells are precursors of osteoclasts, it is possible that FKBP5 overexpression might lead to osteoporosis by affecting osteoclastogenesis. We therefore explore the influences of FKBP5 in osteoclast differentiation. METHODS: Stable transfectants of RAW264.7 overexpressing murine FKBP5 gene were established. Osteoclast differentiation was induced by receptor activator of nuclear factor kappa B (NF-κB) ligand and was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and pit formation assay. RESULTS: FKBP5 transfectants of RAW264.7 generated higher numbers of TRAP-positive multinucleated cells with increased activity of pit formation on calcium phosphate-coated culture slides than mock transfectants. The enhancement of osteoclast differentiation of FKBP5 transfectants was only partially inhibited by N-acetyl L-cysteine. Finally, glucocorticoid enhanced FKBP5 mRNA expression as well as osteoclast differentiation of RAW264.7 cells in a dose-dependent manner. CONCLUSIONS: These results indicate that FKBP5 promotes osteoclast differentiation by a mechanism distinct from NF-κB activation. Moreover, the data suggest that FKBP5 might play a role in bone destruction and development of osteoporosis in RA as well as in glucocorticoid-induced osteoporosis.
21466780 [Level of evidence for therapeutic drug monitoring of low dose methotrexate in inflammator 2011 Jan Methotrexate is prescribed to low-dose, ranging from 7.5 mg to 15 mg and until 25 mg if necessary, pulse once a week, in inflammatory pathologies, in particular in rheumatoid arthritis and psoriasis. The therapeutic answer and the frequency of adverse reactions are very variable from a patient to the other one, consequences of a large interindividual variability of the pharmacokinetic parameters of methotrexate, in particular bioavailability, suggesting a genetic support. Numerous polymorphisms being involved (carriers of influx and efflux, enzymes of the metabolism and of the mechanism of action of methotrexate), their determination with the aim of an individualized prescription does not seem realistic at the moment. On the other hand, an exposure-effect relationship, not so much by considering the plasma concentrations of methotrexate, but those of its polyglutamate derivatives in red blood cells, was described. Their determination should be able to contribute to a faster adaptation of dosages, or to a well-argued change of molecule in case of non clinical response. Although other studies are necessary to specify which markers would be the most relevant, which would be the best moment for their determination and to refine the therapeutic range, this approach seems promising. But currently, the level of proof of the therapeutic drug monitoring of low dose methotrexate in inflammatory disease was classified "remaining to evaluate".
21701336 Development of a brief, 12-item version of the Michigan Hand Questionnaire. 2011 Jul BACKGROUND: The Michigan Hand Questionnaire is one of the most widely used hand-specific surveys that measure health status relevant to patients with acute and chronic hand disorders. However, item redundancy exists in the original version, and an abbreviated survey could minimize responder burden and offer broader applicability. METHODS: Patients (n = 422) with four specific hand conditions--rheumatoid arthritis (n = 162), thumb carpometacarpal osteoarthritis (n = 31), carpal tunnel syndrome (n = 97), and distal radius fracture (n = 132)--completed the Michigan Hand Questionnaire at two time points. Correlation analysis identified two items from each of six domains (i.e., function, activities of daily living, work, pain, aesthetics, and satisfaction). The Brief Michigan Hand Questionnaire score was calculated as the sum of the responses to the 12 items. Psychometric analysis was performed to describe the reliability, validity, and responsiveness of the Brief Michigan Hand Questionnaire. RESULTS: The Brief Michigan Hand Questionnaire includes 12 items that were highly correlated with the summary Michigan Hand Questionnaire score (r = 0.99, p < 0.001). The Brief Michigan Hand Questionnaire scores were highly correlated between the two time periods (r = 0.78, p < 0.001) and by disease type. Responsiveness of the Brief Michigan Hand Questionnaire was high for all diseases and similar to that of the original Michigan Hand Questionnaire. CONCLUSIONS: The 12-item Brief Michigan Hand Questionnaire is an efficient and versatile outcomes instrument specific to hand disability that retains the psychometric properties of the original Michigan Hand Questionnaire. The Brief Michigan Hand Questionnaire is an important tool with which to measure patient outcomes and the quality of care in hand surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, I.(Figure is included in full-text article.).
22046778 [Bone mineral density in patients with rheumatoid arthritis]. 2011 Jul Patients with rheumatoid arthritis (RA), an immune-mediated inflammatory rheumatic disease with peripheral and systemic involvement, are at increased risk of bone loss and fractures. There are many reasons for the high prevalence of osteoporosis (OP) in RA, including both traditional and specific risk factors such as pain and loss of joint function, medication (corticosteroids, methotrexate), and increased proinflammatory cytokines. AIM: To evaluate bone mineral density status in RA patients, focusing on potential relation with classical risk factors for OP. MATERIAL AND METHODS: One-year prospective observational study on 83 consecutive postmenopausal women, 43 diagnosed with RA (group I), and 40 healthy controls (group II) with no previous condition and medication known to affect bone metabolism and turnover. Bone mineral density (BMD) and T-score evaluated by dual X-ray absorbtiometry (DXA) at three standard skeletal sites (L1-L4 lumbar spine, hip and forearm) (Hologique QDR 100 device), and classical risk factors for osteoporosis were assessed in all patients according to a predefined protocol. Data were analyzed in SPSS-13 using ANOVA, t-Student, chi-square and ROC (Receiver Operator Characteristic). RESULTS: Decreased BMD was reported in the majority of RA cases, mainly in the spine and femoral neck (86%), but also in total hip (72%); moreover, osteoporosis was commonly demonstrated in lumbar spine and osteopenia at hip level. Statistically significant differences between diagnostic categories (normal, osteopenia, osteoporosis, WHO 1994) (p<0.05), while no significant differences between mean BMD levels in women with and without RA at different skeletal sites were found (t-student, p>0.05). However, considerable BMD variation (51.7% to 102.3%) was suggested in RA as compared to non-RA patients (14.3% to 27%) (ANOVA). Significant differences in mean T-score at total hip and forearm (mainly 33% radius) were noted in patients with and without RA (p<0.05). No relation between osteodensitometric parameters and classical risk factors for OP has been identified in RA, except menopause. Indirect weak statistically significant correlations were found between mean T-score and menopause duration at all skeletal levels (Pearson's rank correlation, p<0.05), except for the femoral neck (r=+0.03, p<0.05). CONCLUSIONS: Decreased BMD is commonly seen in RA patients. Several characteristics based on DXA assessment have been identified, including preference for distinct skeletal sites (spine, hip, distal forearm), and the particular intervention of menopause.
21949007 Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis an 2012 Feb OBJECTIVE: To evaluate efficacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed. METHODS: The rapid onset and systemic efficacy study was a 24-week, randomised, double-blind trial. Patients were randomly assigned 2:1 to tocilizumab 8 mg/kg (n=412) or placebo (n=207) every 4 weeks while continuing background DMARD in both groups. RESULTS: The primary efficacy endpoint, percentage of patients achieving ACR50 response at week 24, was higher with tocilizumab versus placebo (30.1% vs 11.2%; p<0.0001). Percentages of ACR20 and ACR50 responders were significantly higher with tocilizumab versus placebo as early as week 4 and continued to week 24; more patients in the tocilizumab versus placebo group also achieved ACR70 responses beginning at week 8 (p<0.01). Significant improvements associated with tocilizumab versus placebo were seen in routine assessment of patient index data responses, EULAR good response, DAS28 and percentages of patients achieving low disease activity and clinical remission (based on DAS28). A substudy examining early response to therapy showed improved patient global assessment of disease activity (p=0.005) and pain (p=0.01) and DAS28 (p=0.007) with tocilizumab versus placebo at day 7. Safety findings were consistent with the known tocilizumab safety profile; rates of serious infections (per 100 patient-years) were 7.87 (95% CI 4.30 to 13.2) and 1.20 (95% CI 0.03 to 6.66) in the tocilizumab and placebo groups, respectively. CONCLUSIONS: This study demonstrated the efficacy of tocilizumab in improving measures of disease activity in patients with RA who failed to respond adequately to DMARD therapy. Rapid improvement in clinical outcomes was demonstrated in a substudy as early as week 1 as shown by DAS28 scores, patient measures and C-reactive protein. TRIAL REGISTRY NO: NCT00531817.
21464671 Routine screening for HIV in rheumatology practice. 2011 Apr The rheumatologic manifestations of human immunodeficiency virus (HIV) infection have been recognized since the early days of the epidemic and are characteristic of this disorder. It has been noted that the clinical spectrum of rheumatic disorders in patients with HIV infection has changed since the advent of highly active antiretroviral therapy (HAART) in the mid-1990s. Furthermore, HIV infection may become clinically apparent in rheumatic disease patients during or after they are treated with immunosuppressive therapy. The emergence of manifestations of HIV infection may develop during or after such therapy and may be confused with clinical manifestations known to be associated with the underlying rheumatic disease. In patients with established rheumatologic disease, it is difficult to consider the diagnosis of HIV especially in individuals with few or no known risk factors. In this review, we report 2 cases with established systemic rheumatic disease who developed complications originally thought to be secondary to the underlying inflammatory disorder or antirheumatic therapy. Ultimately, both patients were found to be HIV positive. Recognition of the overlapping signs or symptoms of systemic rheumatic diseases, antirheumatic therapy, and HIV infection can be lifesaving. We propose that all patients with systemic rheumatic diseases, especially those receiving or being considered for disease-modifying antirheumatic therapy, be evaluated systematically for the presence of HIV, taking into consideration the recent Centers for Disease Control and Prevention recommendations for routine opt-out HIV screening in all healthcare settings for those aged 13 to 64 years.
23421098 [Marihuana and cannobinoids as medicaments]. 2012 Biological activity of cannabinoids is caused by binding to two cannabinoid receptors CB1 and CB2. Psychoactive is not only tetrahydrocannabinol (THC) but also: cannabidiol, cannabigerol or cannabichromen. Formerly, the usefulness of hemp was assessed in the relation to temporary appeasement of the symptoms of some ailments as nausea or vomiting. Present discoveries indicates that cannabis-based drugs has shown ability to alleviate of autoimmunological disorders such as: Multiple sclerosis (MS), Rheumatoid arthritis (RA) or inflammatory bowel disease. Another studies indicates that cannabinoids play role in treatment of neurological disorders like Alzheimer disease or Amyotrophic lateral sclerosis (ALS) or even can reduce spreading of tumor cells. Cannabinoids stand out high safety profile considering acute toxicity, it is low possibility of deadly overdosing and side-effects are comprise in range of tolerated side-effects of other medications. In some countries marinol and nabilone are used as anti vomiting and nausea drug. First cannabis-based drug containg naturally occurring cannabinoids is Sativex. Sativex is delivered in an mucosal spray for patients suffering from spasticity in MS, pain relevant with cancer and neuropathic pain of various origin. Despite the relatively low acute toxicity of cannabinoids they should be avoid in patients with psychotic disorders, pregnant or breastfeeding woman. Cannabinoids prolong a time of reaction and decrease power of concentration that's why driving any vehicles is forbidden. Cannabis side-effects varies and depend from several factors like administrated dose, rout of administration and present state of mind. After sudden break from long-lasting use, withdrawal symptoms can appear, although they entirely disappear after a week or two.
21068094 Anti-citrullinated protein antibodies have a low avidity compared with antibodies against 2011 Feb OBJECTIVES: Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA) and have been implicated in disease pathogenesis. Recent ongoing evidence indicates that the ACPA response broadens before precipitation of full-blown RA, as indicated by a more extensive isotype usage and an increased citrullinated epitope recognition profile. Nonetheless, the evolution of the ACPA response is still poorly understood and might intrinsically differ from the protective responses against pathogens. METHODS: The avidity and the avidity maturation of ACPA in relation to the avidity of antibodies against recall antigens were analysed. RESULTS: The avidity of ACPA was significantly lower than the avidity of antibodies to the recall antigens tetanus toxoid and diptheria toxoid. Moreover, ACPA did not show avidity maturation during longitudinal follow-up and ACPA avidity was also relatively low in patients who displayed extensive isotype switching. CONCLUSIONS: These observations indicate that the natural evolution of ACPA differs from the development of antibodies against recall antigens. These data also indicate that ACPA avidity maturation and isotype switching are disconnected, whereby extensive isotype switching occurs in the setting of restricted avidity maturation. Intrinsic differences between the RA-specific autoantibody system and protective antibody responses against pathogens could be of relevance for designing novel B cell-targeted therapies for RA.
21155043 The correlation between increased serum concentrations of interleukin-6 family cytokines a 2011 Jan PURPOSE: This study was performed to determine whether the serum concentrations of interleukin (IL)-6 family cytokines are elevated in patients with rheumatoid arthritis (RA) and to investigate the relationship between IL-6 family cytokine levels and disease activity in RA patients. MATERIALS AND METHODS: We obtained serum samples from 40 patients with RA and 40 age- and sex- matched healthy controls, and we assessed the clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP) levels. Serum samples from five patients with high disease activity (DAS28 > 5.1) were also collected at the eighth week of treatment. Serum concentrations of IL-6, IL-11, and leukemia inhibitory factor (LIF) were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum concentrations of IL-6 family cytokines, including IL-6, IL-11, and LIF, were significantly elevated in patients with RA compared to those of healthy controls. Although there was no significant relationship between IL-6 family cytokine levels and DAS28, the IL-6 levels of patients with RA showed a significant correlation with CRP levels. After eight weeks of medical treatment in patients with high disease activity, a decrease in DAS28 was associated with a significant decrease in the serum concentrations of IL-6 and IL-11. CONCLUSION: The serum concentrations of IL-6 family cytokines were significantly elevated in patients with RA, and they decreased with medical treatment. These findings suggest a possible role for IL-6 family cytokines in the pathogenesis of RA.
22885734 Tacrolimus down-regulates chemokine expressions on rheumatoid synovial fibroblasts: screen 2012 Dec OBJECTIVE: Although the effects of tacrolimus on T cells are well-known, direct effects on rheumatoid synovial fibroblasts (RSF) remain unclear. We studied the effects of tacrolimus on RSF by a DNA microarray analysis. MATERIALS AND METHODS: Tacrolimus and interleukin (IL)-1β were added to cultured RSF. Total RNA was prepared from the cells and the gene expression profile was analyzed by a DNA microarray screening system. mRNA expressions influenced by tacrolimus in the screening system were confirmed by real-time PCR. The effects of tacrolimus on nuclear translocation of nuclear factor-κB (NF-κB) were also examined. RESULTS: The mRNA expressions of CCL3, CCL4, and CXCL8 were up-regulated by IL-1β and down-regulated by tacrolimus. The levels of these IL-1β-induced chemokines in culture supernatant were decreased by a therapeutic concentration of tacrolimus. Tumor necrosis factor-α as well as IL-1β induced these chemokines, while tacrolimus inhibited their production and mRNA expression. Chemotaxis of polymorphonuclear cells in response to IL-1β was also inhibited by tacrolimus. Nuclear translocation of p50 and p65 NF-κB in response to IL-1β was decreased by tacrolimus. CONCLUSION: IL-1β-induced chemokine expressions were down-regulated by tacrolimus, suggesting that tacrolimus exerts its anti-inflammatory effect partly through inhibiting chemokine production by RSF.