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ID PMID Title PublicationDate abstract
25498205 Dry mouth: a critical topic for older adult patients. 2015 Jan PURPOSE: Diminished salivary flow, or dry mouth impacts the oral health of many older adults, dentate and edentulous. As a result typical oral conditions can prove more challenging to both the patient's comfort and home care and the treatment selected by the clinician. This paper will review issues of dry mouth from a clinical and symptomatic perspective and will include the condition's causes, treatment and prevention. STUDY SELECTION: We performed a review of PubMed using the words: older adults, dry mouth, xerostomia, radiation-induced xerostomia, and salivary gland hypofunction. We selected 90 articles with a clinical application perspective. RESULTS: When it comes to treatment of dry mouth conditions, either objective or subjective, there are no easy answers as to the best course of action for a specific individual. While most of the cited studies have examined the most difficult cases of dry mouth (e.g., Sjögren's syndrome, and that seen during and post head and neck cancer treatments), there are many older adults who demonstrate dry mouth from the use of multiple medications. This paper presents a summary of the etiology, diagnosis, prevention, and pharmacological and non-pharmacological treatment of dry mouth (salivary hypofunction and xerostomia in older adults). CONCLUSIONS: It is important to understand the causes of dry mouth and to educate our patients. Starting a prevention program as early as possible considering the most practical, cost effective and efficient treatments with the best risk-benefit ratio will help to diminish dry mouth symptoms and sequelae.
25018831 Possible macrophage activation syndrome following initiation of adalimumab in a patient wi 2014 Macrophage activation syndrome (MAS) has been rarely reported in the course of adult-onset Still's disease (AOSD) and in the majority of cases, it was triggered by an infection. Here, we report, to our knowledge, the first case of MAS occurring after adalimumab treatment initiation and not triggered by an infection. A 26-yearold woman with classical features of AOSD developed persistent fever, severe bicytopenia associated with extreme hyperferritinemia, hyponatremia and abnormal liver function tow months after the initiation of adalimumab treatment. The diagnosis of MAS was made without histological proof. The patient was treated with methylprednisolone pulse therapy and her condition improved. During the disease course, extensive studies could not identify any viral infection or other known underlying etiology for the reactive MAS. The adalimumab was incriminated in this complication. Currently, the patient is in remission on tocilizumab and low-dose prednisolone.
24943141 Pellagra in a patient with primary Sjögren's syndrome. 2014 Jun 18 A 27-year-old woman presented with persistent dryness of the mouth and eyes. She presented with permanent photodistributed rash involving the face and distal extremities. Laboratory tests showed positive Sjögren's syndrome (SS)-A and SS-B antibodies. Histological examination of minor salivary gland biopsy revealed inflammatory infiltration grade 4 according to Chisholm's classification. Skin biopsy showed acanthosis, hyperkeratosis in the epidermis and little inflammatory infiltrate in the dermis. There was an infiltration of CD4 T lymphocytes in the dermis. Based on the characteristics of the dermatitis and on a rapid response to niacin replacement, the diagnosis of pellagra was carried out. A complete resolution of the dermatological signs was obtained within 2 months. To the best of our knowledge, the association between primary SS and pellagra has never been reported. We emphasise the possible mechanisms of this association.
22658853 Cystic lung lesions in Sjogren syndrome: analysis of lymphocyte subsets in tissue with cli 2013 Feb Pulmonary complications associated with Sjögren syndrome (SS) have attracted attention in recent years. Sjögren syndrome has been associated with small cyst formation in salivary glands, thymus, and lungs and has been recently brought to the forefront by radiologists due to high-resolution techniques. However, pathologists are less aware of this finding unless clinico-radiologic-pathologic correlation is sought. Formation of large bullae in SS is a rare complication with potential for confusion with other diseases. Here, we present the clinical, radiologic, and pathologic findings in 3 patients with SS associated with multiple pulmonary cystic lesions. All 3 patients had a variable mixed restrictive and obstructive component of the disease. There was good correlation with the pulmonary function tests (PFTs), high-resolution computed tomographic scan, and morphology with regard to the restrictive component. The small cysts appear to correlate with the extent of obstructive changes on the PFTs. However, the large bullae do not, implying noncommunication with the conducting airways. This noncorrelation between the PFTs and extent of bullous disease with predominant involvement of lower lobes in SS enables distinction from bullous emphysema. The mechanism of bulla formation in SS appears to be different from bullous emphysema. A check valve mechanism has been proposed previously in SS, which does not explain cyst formation in the thymus. Alternately, inflammation may play a role with the key suspects being CD4 T-helper cells and perhaps NK cells. This is the first report of a clinico-radiologic-pathologic correlation with analysis of lymphocyte subsets.
25167870 Acute transverse myelitis and psoriasiform dermatitis associated with Sjoegren's syndrome: 2014 Aug 29 BACKGROUND: Clinical complications of Sjoegren's syndrome include myelitis and skin manifestations. There is scarce observational data and a lack of randomised controlled studies regarding the treatment of Sjoegren's syndrome in the presence of such complications. CASE PRESENTATION: Here we report the case of a 41-year-old Caucasian female patient with biopsy-proven Sjoegren's syndrome who initially presented with generalized exanthema and subsequently developed acute extensive transverse myelitis. In view of the rapid deterioration we opted for an intensive treatment using a combination of corticosteroid pulse therapy, plasmapheresis and cyclophosphamide, which we later changed to rituximab. Under that treatment the skin manifestations resolved entirely whereas transverse myelitis showed incomplete remission. CONCLUSION: Severe neurological and dermatological complications may occur in Sjoegren's syndrome. This suggests a close yet currently unclear pathogenetic relationship. Intensive immunosuppressant treatment resulted in significant improvement of both symptom clusters. Skin manifestations may precede other severe complications in Sjoegren's syndrome and therefore require particular attention.
25146603 Traditional Chinese medicine compound ShengJinRunZaoYangXue granules for treatment of prim 2014 BACKGROUND: Traditional Chinese medical treatment of primary Sjögren's syndrome has advantages over Western medicine in terms of fewer side effects and improved patient conditions. This study was a multicenter, randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of ShengJinRunZaoYangXue granules for the treatment of primary Sjögren's syndrome, including the symptoms of dry mouth and dry eye. METHODS: We undertook a 6-week, double-blind, randomized trial involving 240 patients with primary Sjögren's syndrome at five centers in East China. A computer-generated randomization schedule assigned patients at a 2:1 ratio to receive either ShengJinRunZaoYangXue granules or placebo once daily. Patients and investigators were blinded to treatment allocation. The primary endpoints were the salivary flow rate, Schirmer test results, and sugar test results. Intention-to-treat and per-protocol analyses were performed. RESULTS: All 240 patients were randomly allocated to either the treatment group (n = 160, ShengJinRunZaoYangXue granules) or placebo group (n = 80) and were included in the intention-to-treat analysis. After program violation and loss to follow-up, a total of 199 patients were included in the per-protocol analysis. At six week, intention-to-treat and per-protocol analyses of the left-eye Schirmer I test results showed an improved difference of 1.36 mm/5 min (95% CI: 0.03 to 2.69 mm/5 min) and 1.35 mm/5 min (95% CI: 0.04 to 2.73 mm/5 min), respectively, and those of the right-eye Schirmer I test results showed an improved difference of 1.12 mm/5 min (95% CI: 0.02 to 2.22 mm/5 min) and 1.12 mm/5 min (95% CI: -0.02 to 2.27 mm/5 min), respectively. There was no significant difference between the two groups before treatment. After treatment, the between-group and within-group before-and-after paired comparison results were statistically significant (P < 0.05). Intention-to-treat and per-protocol analyses showed an improved salivary flow rate by 0.04 ml/15 min (95% CI: -0.49 to 0.58 ml/15 min) and 0.04 ml/15 min (95% CI: -0.52 to 0.60 ml/15 min), respectively, but the differences were not significant. Intention-to-treat and per-protocol analyses showed that the sugar test results were improved by 1.77 minutes (95% CI: 0.11 to 3.44 minutes) and 1.84 minutes (95% CI: 0.12 to 3.55 minutes), respectively, but the differences were not significant. For the secondary endpoint, intention-to-treat and per-protocol analyses showed significant improvement in the integrated evaluation of treated patients with dry eye and dry mouth after six weeks of treatment. The incidence of adverse events was 15.6% in the treatment group and 10.0% in the placebo group. Most (94%) adverse events were mild to moderate in the two groups, and only two cases of serious adverse events occurred in the treatment group; both were caused by autoimmune liver disease. CONCLUSIONS: Six-week treatment with ShengJinRun ZaoYangXue granules for primary Sjögren's syndrome in this large-scale study improved the symptoms of dry mouth, dry eyes, and low tear flow rate with minimal adverse events.
25651660 Lupus coagulopathy post-tasing: a case study. 2014 Nov While severe adverse effects are rare, evidence suggests significant physiological effects may be associated with the use of electrical incapacitation devices, or TASERs. In this case, a 28 year old Caucasian female with chronic, stable systemic lupus erythematosus (SLE) was voluntarily tased in a work-related training procedure. Days later, she presented to the emergency room with an acute flare of her lupus and a constellation of symptoms that lead to new diagnoses of antiphospholipid syndrome (APS), Raynaud phenomenon, acute lower left extremity deep vein thrombosis (DVT), and diffuse bilateral pulmonary emboli (PEs). Due to the temporal relationship of these complications and this patient's history of autoimmune disorders, it is reasonable to believe that an APS was both induced by the tasing event and associated with her lupus.
25159733 Tear proteomic analysis of Sjögren syndrome patients with dry eye syndrome by two-dimensi 2014 Aug 27 We examined the tear film proteome of patients with Sjögren's syndrome (SS) and dry eye syndrome (group A), patients with dry eye symptoms (group B) and normal volunteers (group C). Tear samples were pooled from 8 subjects from each group and were subjected to two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry (2D-nano-LC-MS/MS). The tear breakup time for group A was significantly reduced compared with group B and C (P < 0.001). Group A (Schirmer I test, 2.13 ± 2.38 mm/5 min) had markedly lower tear volume than group B (5.94 ± 4.75 mm/5 min) and C (14.44 ± 6.57 mm/5 min) (P < 0.001). Group A had significantly higher normalized tear protein content (1.8291 ± 0.2241 μg/mm) than group B (1.0839 ± 0.1120 μg/mm) (P = 0.001) and C (0.2028 ± 0.0177 μg/mm) (P = 0.001). The 2D-nano-LC-MS/MS analysis identified a total of 435 proteins, including 182 (54.8%), 247 (74.4%) and 278 (83.7%) in group A, B, and C, respectively, with 56 (16.7%) proteins including defensin α1, clusterin and lactotransferrin unique to group A. In conclusion, dry eye syndrome in SS patients is associated with an altered proteomic profile with dysregulated expression of proteins involved in a variety of important cellular process including inflammation, immunity, and oxidative stress.
24803230 Lack of association of vitamin D receptor gene polymorphisms/haplotypes in Sjögren's synd 2015 Feb The vitamin D is involved in a wide variety of biological processes including bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation. Vitamin D has several immunomodulatory effects through vitamin D receptor (VDR). A series of common single-nucleotide polymorphisms (SNPs) in the vitamin D receptor gene have been linked to numerous of diseases, including osteoarthritis, diabetes, cancer, cardiovascular diseases, tuberculosis, virus infections, urinary stones, and periodontitis. Several studies have reported that genetic variations of VDR might be a risk factor for the development of autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), psoriasis, and autoimmune thyroid diseases (AITD). However, no data is available on the possible relationship between primary Sjögren's syndrome and VDR gene polymorphisms. Our aim was to determine VDR gene BsmI, ApaI, TaqI, and FokI polymorphism genotypes in pSS patients and healthy controls to analyze whether a relationship exists between polymorphisms in the VDR gene and susceptibility to Sjögren's syndrome. In the current study, 105 patients with pSS and 93 healthy controls were tested for VDR gene polymorphisms (BsmI, ApaI, TaqI, and FokI) genotypes. There were no statistical differences in the distribution of BsmI, TaqI, ApaI, and FokI genotypes and the common haplotypes between pSS patients and healthy controls. We hypothesized that the TaqI, BsmI, ApaI, and FokI polymorphisms of the VDR gene are not associated with the development of primary Sjögren's syndrome in the Hungarian population studied.
24287193 Oral complications of Sjögren's syndrome. 2014 Feb Numerous oral manifestations associated with salivary gland dysfunction, and particularly Sjögren's syndrome, have been reported in the literature. This article discusses the evidence on a wide range of oral manifestations associated with Sjögren's syndrome.
23943735 Nasal and paranasal involvement in primary Sjogren`s syndrome. 2013 Sep BACKGROUND: The aim of this study is to investigate nasal and paranasal signs and symptoms of the primary Sjogren`s syndrome patients and compare them with healthy controls. METHODOLOGY: Seventy-seven (7 M, 70 F) primary Sjogren`s syndrome patients and 77 healthy controls were included in the study. Anterior rhinoscopy, nasal endoscopy, 5 component smell discrimination test, nasal clearance analysis with saccharin test and electrorhinomanometer were performed. RESULTS: Nasal crusting was present in 31 and 24 individuals in patient and control groups, respectively. Sinusitis was present in 2 and 1 individuals in patient and control groups, respectively. Nasal polyposis was present in 7 and 1 individuals in patient and control groups, respectively. These differences were not statistically different. CONCLUSION: Although there were some findings in a few patients, nasal findings were insignificant and mild even in patients with severe oral or ocular findings. Rhinomanometry, nasal clearance determination or smell discrimination tests have very little value in the diagnosis or management of primary Sjogren`s syndrome. Nasal polyposis was higher in the patient group, though it did not reach a significant level. Nasal glandular involvement is mild and insignificant in primary Sjogren`s syndrome.
23759204 Grape seed proanthocyanidin extract has potent anti-arthritic effects on collagen-induced 2013 Sep Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of the synovial joints, joint malformations, and disability. The continuous use of conventional anti-inflammatory drugs is associated with severe adverse effects. Grape seed proanthocyanidin extract (GSPE) is considered to have protective effects against several diseases. In this study based on the mouse adjuvant-induced-arthritis (AIA) model, we examined the effects of GSPE on the key mediators of arthritic inflammation, namely T cell subsets, glucocorticoid-induced tumour necrosis factor receptor (GITR) expressing cells, CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, Th17 cells, Th1/Th2 cytokines, and inflammatory mediator gene expression. We treated BALB/c mice with 25, 50, or 100 mg/kg GSPE or saline daily (14 days) per orally (p.o.) at the onset of AIA. At the peak phase of AIA (day 14), the heparinised whole blood and ankle joints of all groups were collected and tested. GSPE-treated mice showed a substantial reduction in the levels of T cell subsets, GITR-expressing cells, and Th1 cytokines as well as the inflammatory mediators (MCP-1, MIP-2, and ICAM-1) that induce them compared with the vehicle-treated (saline) and arthritic mice. However, GSPE significantly upregulated the number of Tregs and Th2 cytokine producing cell number or it also induced Th17/Treg rebalance and orchestrated various pro-inflammatory and anti-inflammatory cytokines and the gene expression of their mediators that mediate cellular infiltration into the joints. This might, contribute to its anti-arthritic activity. Our results suggest that p.o. treatment with GSPE attenuated AIA in mice might offer a promising alternative/adjunct treatment for RA.
23298137 4-mer hyaluronan oligosaccharides stimulate inflammation response in synovial fibroblasts 2013 4-mer hyaluronan (HA) oligosaccharides stimulate pro-inflammatory effects in different cell types by interacting with both the toll-like receptor-4 (TLR-4) and -2 (TLR-2). This interaction induces the activation of the transforming growth factor activated kinase-1 (TAK-1) that activates the nuclear factor kappaB (NF-kB) either directly and/or through the activation of p38-mitogen-activated protein kinase (p38-MAPK). This in turn induces the transcription of proinflammatory mediators that prime inflammation. Our aim was to investigate the involvement of TAK-1 and p38-MAPK in 4-mer HA oligosaccharide-induced inflammatory response in mouse synovial fibroblasts obtained from normal DBA/J1 mice (NSF) and from mice subjected to collagen-induced arthritis (CIA). Treatment of NSF and rheumatoid arthritis synovial fibroblasts (RASF) with 4-mer HA showed a marked up-regulation of TLR-4, TLR-2, TAK-1 and p38-MAPK mRNA expression and of the related proteins, as well as NF-kB activation. High levels were also detected of TNF-α, IL- 1β, MMP-13 and iNOS. Treatment of NSF and RASF, previously stimulated with 4-mer HA oligosaccharides, with TAK- 1 and/or p38-MAPK specific inhibitors significantly reduced all the parameters, although the inhibitory effect of p38- MAPK was less effective than that of TAK-1. The addition of CD44 antibody to both NSF and RASF showed that CD44 was not involved in 4-mer HA-induced inflammation.
24449579 Brief report: carboxypeptidase B serves as a protective mediator in osteoarthritis. 2014 Jan OBJECTIVE: We previously demonstrated that carboxypeptidase B (CPB) protects against joint erosion in rheumatoid arthritis by inactivating complement component C5a. We also found that levels of CPB are abnormally high in the synovial fluid of individuals with another joint disease, osteoarthritis (OA). We undertook this study to investigate whether CPB plays a role in the pathogenesis of OA. METHODS: We compared the development of OA in CPB-deficient (Cpb2(-/-) ) mice and wild-type mice by subjecting them to medial meniscectomy and histologically assessing cartilage damage, osteophyte formation, and synovitis in the stifle joints 4 months later. We measured levels of proCPB, proinflammatory cytokines, and complement components in synovial fluid samples from patients with symptomatic and radiographic knee OA. Finally, we used enzyme-linked immunosorbent assay, flow cytometry, and hemolytic assays to assess the effect of CPB on formation of membrane attack complex (MAC)-a complement effector critical to OA pathogenesis. RESULTS: Cpb2(-/-) mice developed dramatically greater cartilage damage than did wild-type mice (P < 0.01) and had a greater number of osteophytes (P < 0.05) and a greater degree of synovitis (P < 0.05). In synovial fluid samples from OA patients, high levels of proCPB were associated with high levels of proinflammatory cytokines and complement components, and levels of proCPB correlated positively with those of MAC. In in vitro complement activation assays, activated CPB suppressed the formation of MAC as well as MAC-induced hemolysis. CONCLUSION: Our data suggest that CPB protects against inflammatory destruction of the joints in OA, at least in part by inhibiting complement activation.
24515446 Are anti-CCP antibodies in psoriatic arthritis patients a biomarker of erosive disease? 2014 Sep To determine the frequency of anticyclic citrullinated peptide (CCP) antibodies in a cohort of psoriatic arthritis (PsA) patients and to compare clinical, serological and radiological characteristics between PsA patients with and without anti-CCP antibodies. Patients with PsA, according to classification criteria for PsA, were consecutively recruited from an outpatient rheumatology clinic. Demographic and clinical data were collected in all cases. Serum samples from all patients were analyzed for rheumatoid factor and anti-CCP antibodies. Radiographs of hands and feet were obtained and the presence of erosions was recorded. The study included 81 patients; 43 (53 %) were men, with a median age of 45.7 years (interquartile range (IQR) 39-72) and median disease duration of 9.4 years (IQR 2-14). Anti-CCP antibodies were found in 11 patients (13.5 %), median titer 174.9 U/ml. Polyarticular involvement (72.7 vs. 17.1 %), frequency of erosive disease (72.7 vs. 37.1 %) and use of tumor necrosis factor-α inhibitors (54.5 vs. 28.5 %) were significantly higher in PsA patients with anti-CCP positivity. Anti-CCP negative PsA patients had predominantly more oligoarticular (62.8 vs. 27.2 %) and nail (81.4 vs. 36.3 %) involvement. Presence of enthesitis, dactylitis and Psoriasis Area Severity Index scores were similar in both groups. Anti-CCP antibodies were found in a subset of PsA patients, and their presence was associated with more severe disease phenotype. Further studies in a larger population are needed to define the role of anti-CCP as a biomarker of erosive disease in PsA.
25253467 Tissue specific CD4+ T cell priming determines the requirement for interleukin-23 in exper 2014 Sep 25 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease with striking heterogeneity in (i) clinical presentation, (ii) autoantibody profiles and (iii) responses to treatment suggesting that distinct molecular mechanisms may underlie the disease process. Proteoglycan-induced arthritis (PGIA) is induced by two pathways either by intraperitoneal (i.p.) or subcutaneous (s.c.) exposure to PG. CD4+ T cells primed by the i.p. route are T helper (Th)1 cells expressing interferon gamma (IFN-γ) whereas CD4+ T cells primed by the s.c. route are Th17 cells expressing interleukin (IL)-17. IL-23 is necessary for maintaining the phenotype of Th17 cells; however, IL-23 is inflammatory independent of IL-17. The aim of this study was to determine if PGIA induced by different routes of immunization is dependent on IL-23. METHODS: BALB/c wild type (WT), IL-12p40-/- and IL-23p19-/- littermate mice were immunized with recombinant G1 (rG1) domain of human PG in adjuvant either i.p. or s.c. and development of arthritis monitored. Joint histology was assessed. CD4+ T cell cytokines in spleen, lymph node (LN), and joint were assessed by intracellular staining and cytokine enzyme-linked immunosorbent assay. RNA transcripts for cytokines and transcription factors were examined. RESULTS: PGIA was suppressed in the p40-/- and p19-/- mice immunized by the s.c. route but only inhibited in p40-/- mice by the i.p. route. The joints of s.c. but not i.p. sensitized mice contained a population of CD4+ T cells expressing single positive IFN-γ and IL-17 and double positive IFN-γ/IL-17 which were dependent on IL-23 expression. The IFN-γ and IL-17 response in spleen and inguinal LN was inhibited in p19-/- mice and p40-/- mice after s.c. immunization, whereas in i.p. immunized p19-/- mice, IL-17 but not IFN-γ was reduced. Inguinal LN CD11c+ dendritic cells (DC) from s.c. immunized, but not spleen DC from i.p. immunized mice, produced IL-23, IL-1β, and IL-6 and activated T cells to produce IL-17. CONCLUSION: IL-23 is necessary for the activity of Th17 after s.c. immunization and does not play a role independent of IL-17 after i.p. immunization. These data demonstrate that the molecular pathways IL-23/17 and IL-12/IFN-γ may represent subtypes of arthritis determined by the mode of induction.
25144740 SH3BP2 gain-of-function mutation exacerbates inflammation and bone loss in a murine collag 2014 OBJECTIVE: SH3BP2 is a signaling adapter protein which regulates immune and skeletal systems. Gain-of-function mutations in SH3BP2 cause cherubism, characterized by jawbone destruction. This study was aimed to examine the role of SH3BP2 in inflammatory bone loss using a collagen-induced arthritis (CIA) model. METHODS: CIA was induced in wild-type (Sh3bp2(+/+)) and heterozygous P416R SH3BP2 cherubism mutant knock-in (Sh3bp2(KI/+)) mice, an SH3BP2 gain-of-function model. Severity of the arthritis was determined by assessing the paw swelling and histological analyses of the joints. Micro-CT analysis was used to determine the levels of bone loss. Inflammation and osteoclastogenesis in the joints were evaluated by quantitating the gene expression of inflammatory cytokines and osteoclast markers. Furthermore, involvement of the T- and B-cell responses was determined by draining lymph node cell culture and measurement of the serum anti-mouse type II collagen antibody levels, respectively. Finally, roles of the SH3BP2 mutation in macrophage activation and osteoclastogenesis were determined by evaluating the TNF-α production levels and osteoclast formation in bone marrow-derived M-CSF-dependent macrophage (BMM) cultures. RESULTS: Sh3bp2(KI/+) mice exhibited more severe inflammation and bone loss, accompanying an increased number of osteoclasts. The mRNA levels for TNF-α and osteoclast marker genes were higher in the joints of Sh3bp2(KI/+) mice. Lymph node cell culture showed that lymphocyte proliferation and IFN-γ and IL-17 production were comparable between Sh3bp2(+/+) and Sh3bp2(KI/+) cells. Serum anti-type II collagen antibody levels were comparable between Sh3bp2(+/+) and Sh3bp2(KI/+) mice. In vitro experiments showed that TNF-α production in Sh3bp2(KI/+) BMMs is elevated compared with Sh3bp2(+/+) BMMs and that RANKL-induced osteoclastogenesis is enhanced in Sh3bp2(KI/+) BMMs associated with increased NFATc1 nuclear localization. CONCLUSION: Gain-of-function of SH3BP2 augments inflammation and bone loss in the CIA model through increased macrophage activation and osteoclast formation. Therefore, modulation of the SH3BP2 expression may have therapeutic potential for the treatment of rheumatoid arthritis.
23983789 Microarray analysis reveals the molecular basis of antiarthritic activity of huo-luo-xiao- 2013 Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune origin. Huo-luo-xiao-ling dan (HLXL) is an herbal mixture that has been used in traditional Chinese medicine over several decades to treat chronic inflammatory diseases including RA. However, the mechanism of the anti-arthritic action of this herbal remedy is poorly understood at the molecular level. In this study, we determined by microarray analysis the effects of HLXL on the global gene expression profile of the draining lymph node cells (LNC) in the rat adjuvant arthritis (AA) model of human RA. In LNC restimulated in vitro with the disease-related antigen mycobacterial heat-shock protein 65 (Bhsp65), 84 differentially expressed genes (DEG) (64 upregulated and 20 downregulated) versus 120 DEG (94 upregulated and 26 downregulated) were identified in HLXL-treated versus vehicle (Water)-treated rats, respectively, and 62 DEG (45 upregulated and 17 downregulated) were shared between the two groups. The most affected pathways in response to HLXL treatment included immune response, inflammation, cellular proliferation and apoptosis, and metabolic processes, many of which are directly relevant to arthritis pathogenesis. These results would advance our understanding of the mechanisms underlying the anti-arthritic activity of HLXL.
23901289 No impact of tumor necrosis-factor antagonists on the joint manifestations of sarcoidosis. 2013 OBJECTIVE: The use of anti-tumor necrosis factor (TNF) agents to treat joint manifestations of sarcoidosis has not been described. We evaluated the efficacy and safety of three such biologics in patients with these symptoms refractory to conventional therapy (nonsteroidal anti-inflammatory drugs, corticosteroids, and/or disease-modifying antirheumatic drugs). METHODS: This retrospective study, covering January 2001 to September 2011, examined clinical-biological parameters collected before anti-TNF treatment (age, sex, duration of disease evolution, drugs taken), and at introduction and under anti-TNF therapy (number of painful and swollen joints, visual analog scale score of global disease activity, disease-activity score of 28 joints with erythrocyte sedimentation rate or C-reactive protein, TNF-antagonist duration). At 3, 6, and 12 months, anti-TNF impact on joints and the therapeutic response according to European League Against Rheumatism criteria used for rheumatoid arthritis were assessed. RESULTS: Ten patients' data were evaluated; some of them had received several anti-TNF agents (median [range] duration on each biotherapy was 10 [4-30] months), which enabled analysis of 19 prescriptions. The total duration of anti-TNF exposure was 17.6 patient-years, which was started a median of 3 (0.33-17) years after sarcoidosis diagnosis. The median numbers of painful and swollen joints were 1 (0-28) and 0 (0-9), respectively. Despite rapid efficacy, after 1 year of treatment, clinical (especially joint) and biological parameters were comparable to pretreatment, and only the corticosteroid dose was significantly lower (P=0.03). One case of mild skin toxicity was noted. CONCLUSION: TNF antagonists allowed significant steroid sparing and were well tolerated, but do not seem to be effective against sarcoidosis joint involvement.
27790020 Efficacy and tolerability of naproxen/esomeprazole magnesium tablets compared with non-spe 2013 Non-steroidal anti-inflammatory drugs (NSAIDs), such as non-selective NSAIDs (nsNSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors, are commonly prescribed for arthritic pain relief in patients with osteoarthritis (OA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS). Treatment guidelines for chronic NSAID therapy include the consideration for gastroprotection for those at risk of gastric ulcers (GUs) associated with the chronic NSAID therapy. The United States Food and Drug Administration has approved naproxen/esomeprazole magnesium tablets for the relief of signs and symptoms of OA, RA, and AS, and to decrease the risk of developing GUs in patients at risk of developing NSAID-associated GUs. The European Medical Association has approved this therapy for the symptomatic treatment of OA, RA, and AS in patients who are at risk of developing NSAID-associated GUs and/or duodenal ulcers, for whom treatment with lower doses of naproxen or other NSAIDs is not considered sufficient. Naproxen/esomeprazole magnesium tablets have been compared with naproxen and celecoxib for these indications in head-to-head trials. This systematic literature review and network meta-analyses of data from randomized controlled trials was performed to compare naproxen/esomeprazole magnesium tablets with a number of additional relevant comparators. For this study, an original review examined MEDLINE(®), Embase(®), and the Cochrane Controlled Trials Register from database start to April 14, 2009. Using the same methodology, a review update was conducted to December 21, 2009. The systematic review and network analyses showed naproxen/esomeprazole magnesium tablets have an improved upper gastrointestinal tolerability profile (dyspepsia and gastric or gastroduodenal ulcers) over several active comparators (naproxen, ibuprofen, diclofenac, ketoprofen, etoricoxib, and fixed-dose diclofenac sodium plus misoprostol), and are equally effective as all active comparators in treating arthritic symptoms in patients with OA, RA, and AS. Naproxen/esomeprazole magnesium tablets are therefore a valuable option for treating arthritic symptoms in eligible patients with OA, RA, and AS.