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ID PMID Title PublicationDate abstract
25253568 Serum ferritin level correlates with SLEDAI scores and renal involvement in SLE. 2015 Jan INTRODUCTION: Ferritin is an acute-phase reactant that is elevated in various autoimmune disorders. Serum ferritin levels have been positively correlated with disease activity scores of rheumatoid arthritis and systemic lupus erythematosus (SLE). Further, enhanced levels of ferritin have also been reported in lupus nephritis. However, there are no reports from the Indian subcontinent. METHODS: Seventy-six female SLE patients, diagnosed on the basis of revised ACR criteria, and 50 healthy females, age matched from similar geographical areas, were enrolled in the present study. Serum levels of ferritin, IFN-α and IL-6 were quantified by enzyme-linked immunosorbent assay (ELISA). Clinical, biochemical, serological and other markers of disease activity (C3, C4 and anti-dsDNA) were measured by standard laboratory procedure. RESULTS: Serum ferritin levels were significantly higher in SLE patients compared to healthy controls (p < 0.0001). Ferritin levels positively correlated with SLE Disease Activity Index (SLEDAI) (p = 0.001, r = 0.35), anti-dsDNA (p = 0.001, r = 0.35), IFN-α (p < 0.0001, r = 0.51) and IL-6 (p < 0.0001, r = 0.65) and negatively correlated with C3 (p = 0.0006, r = -0.38) and C4 (p = 0.01, r = -0.28). Interestingly, serum levels of ferritin were positively associated with proteinuria (p = 0.001, r = 0.36), serum urea (p = 0.0004, r = 0.39) and serum creatinine (p = 0.0006, r = 0.38). CONCLUSION: Serum ferritin is an excellent marker of disease activity and renal dysfunction in SLE.
25143646 Outcome in primary cemented total knee arthroplasty with or without drain: A prospective c 2014 Jul BACKGROUND: Suction drain insertion is a common practice in orthopedic surgery, especially after joint arthroplasty to prevent the formation of a hematoma. Theoretically the use of a drain should diminish the volume of hematoma; however the literature has conflicting data. Some authors state that drainage evacuates fluid from a limited area only and can be a cause of infection due to retrograde migration of bacteria. It can also impair the early postoperative rehabilitation. The aim of this study was to evaluate the clinical outcome (especially postoperative pain) and intake of analgesics in patients who had undergone primary cemented total knee arthroplasty (TKA) with or without a postoperative drain. MATERIALS AND METHODS: A prospective comparative study of 108 consecutive patients (121 knees) was conducted. They were divided into two groups: A study group, with no drainage and a control group with drain inserted at the end of surgery. A total of 121 patients were recruited into two groups. A study group consisted of 59 knees, in which we did not use drainage after TKA and a control group with 62 knees, in which drain was inserted post surgery. Both groups were comparable in terms of preoperative characteristics. The indication for TKA was osteoarthritis (n = 105) and rheumatoid arthritis (n = 16). RESULTS: In patients without drainage we observed lower need for opioids, higher blood loss on the 1(st) postoperative day and a lower need for change of dressings. There were no statistically significant differences in terms of total blood loss, hidden blood loss, transfusion rate, range of motion, length of hospital stay or incidence of complications between the two groups. In 1 year observation there were no differences in clinical outcome between the two groups. CONCLUSIONS: The present study conclude that there is no rationale for the use of drain after primary TKA. There are benefits in terms of lower opioid intake, lower blood loss on the first postoperative day and lower need for dressing reinforcement during hospitalization.
25101087 Accumulation of VH Replacement Products in IgH Genes Derived from Autoimmune Diseases and 2014 VH replacement refers to RAG-mediated secondary recombination of the IgH genes, which renews almost the entire VH gene coding region but retains a short stretch of nucleotides as a VH replacement footprint at the newly generated VH-DH junction. To explore the biological significance of VH replacement to the antibody repertoire, we developed a Java-based VH replacement footprint analyzer program and analyzed the distribution of VH replacement products in 61,851 human IgH gene sequences downloaded from the NCBI database. The initial assignment of the VH, DH, and JH gene segments provided a comprehensive view of the human IgH repertoire. To our interest, the overall frequency of VH replacement products is 12.1%; the frequencies of VH replacement products in IgH genes using different VH germline genes vary significantly. Importantly, the frequencies of VH replacement products are significantly elevated in IgH genes derived from different autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and allergic rhinitis, and in IgH genes encoding various autoantibodies or anti-viral antibodies. The identified VH replacement footprints preferentially encoded charged amino acids to elongate IgH CDR3 regions, which may contribute to their autoreactivities or anti-viral functions. Analyses of the mutation status of the identified VH replacement products suggested that they had been actively involved in immune responses. These results provide a global view of the distribution of VH replacement products in human IgH genes, especially in IgH genes derived from autoimmune diseases and anti-viral immune responses.
25096914 Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activati 2014 Oct Auranofin is a gold-containing compound classified by the World Health Organization as a clinically established rheumatoid arthritis therapeutic agent. Through drug screening for novel anticancer therapeutics, we unexpectedly identified auranofin as a potent anticancer agent against a p53-null ovarian carcinoma SKOV3 cell line. However, the molecular mechanism underlying auranofin-mediated anticancer activity in ovarian cancer cells is basically unknown. Here, we show that auranofin inhibits proliferation and survival of SKOV3 cells in a dose‑ and time‑dependent manner. Auranofin treatment activates the pro-apoptotic caspase-3, increases protein levels of apoptosis-inducing proteins Bax and Bim and reduces the expression of the anti-apoptotic mediator Bcl-2 in SKOV3 cells. Moreover, auranofin downregulates IκB kinase (IKK)-β and promotes nuclear localization and the activation of FOXO3 tumor suppressor, leading to cellular apoptosis in SKOV3 cells. In contrast, silencing FOXO3 diminishes the pro-apoptotic signaling of auranofin in SKOV3 cells. These results suggest that auranofin may induce caspase-3-mediated apoptosis in a FOXO3-dependent manner. The observed upregulation of pro-apoptotic genes and apoptosis in cancer cells without p53 in response to auranofin suggests a novel p53-independent mechanism underlying auranofin-induced apoptosis in ovarian cancer cells.
25080523 CXCRâ‚„antagonism as a therapeutic approach to prevent acute kidney injury. 2014 Oct 1 We examined whether antagonism of the CXCRâ‚„receptor ameliorates the loss of renal function following ischemia-reperfusion. CXCRâ‚„is ubiquitously expressed on leukocytes, known mediators of renal injury, and on bone marrow hematopoietic stem cells (HSCs). Plerixafor (AMD3100, Mozobil) is a small-molecule CXCRâ‚„antagonist that mobilizes HSCs into the peripheral blood and also modulates the immune response in in vivo rodent models of asthma and rheumatoid arthritis. Treatment with plerixafor before and after ischemic clamping ameliorated kidney injury in a rat model of bilateral renal ischemia-reperfusion. Serum creatinine and blood urea nitrogen were significantly reduced 24 h after reperfusion, as were tissue injury and cell death. Plerixafor prevented the renal increase in the proinflammatory chemokines CXCL1 and CXCL5 and the cytokine IL-6. Flow cytometry of kidney homogenates confirmed the presence of significantly fewer leukocytes with plerixafor treatment; additionally, myeloperoxidase activity was reduced. AMD3465, a monocyclam analog of plerixafor, was similarly renoprotective. Four weeks postreperfusion, long-term effects included diminished fibrosis, inflammation, and ongoing renal injury. The mechanism by which CXCRâ‚„inhibition ameliorates AKI is due to modulation of leukocyte infiltration and expression of proinflammatory chemokines/cytokines, rather than a HSC-mediated effect. The data suggest that CXCRâ‚„antagonism with plerixafor may be a potential option to prevent AKI.
24898360 Risk of stroke in patients with rheumatism: a nationwide longitudinal population-based stu 2014 Jun 5 The aim of this study was to investigate rheumatoid arthritis (RA), and systemic lupus erythematous (SLE) as risk factors for stroke. The study was analyzed by Using the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005), this cohort study investigated patients with a recorded diagnosis of RA (N = 6114), and SLE (N = 621) between January 1, 2004, and December 31, 2007, with age-matched controls (1:4) (for RA, N = 24456; SLE, N = 2484). We used Cox proportional-hazard regressions to evaluate the hazard ratios (HRs) after adjusting confounding factors. Our study found 383 of 6114 RA patients, experienced stroke during the 20267 person-year follow-up period. The adjusted HR of stroke for RA patients was 1.24 (95% CI, 1.11 to 1.39), and for SLE patients was 1.88 (95% CI, 1.08 to 3.27). When steroid was added as additional confounding factor, the adjusted HR of ischemic stroke for RA patients was 1.32 (95% CI, 1.15 to 1.50), and for SLE patients was 1.31 (95% CI, 0.51 to 3.34). In conclusion, the rheumatic diseases of RA, and SLE are all risk factors for stroke. After controlled the effect of steroid prescription, RA is risk factor for ischemic stroke.
24854898 Discovery of binding proteins for a protein target using protein-protein docking-based vir 2014 Oct Target structure-based virtual screening, which employs protein-small molecule docking to identify potential ligands, has been widely used in small-molecule drug discovery. In the present study, we used a protein-protein docking program to identify proteins that bind to a specific target protein. In the testing phase, an all-to-all protein-protein docking run on a large dataset was performed. The three-dimensional rigid docking program SDOCK was used to examine protein-protein docking on all protein pairs in the dataset. Both the binding affinity and features of the binding energy landscape were considered in the scoring function in order to distinguish positive binding pairs from negative binding pairs. Thus, the lowest docking score, the average Z-score, and convergency of the low-score solutions were incorporated in the analysis. The hybrid scoring function was optimized in the all-to-all docking test. The docking method and the hybrid scoring function were then used to screen for proteins that bind to tumor necrosis factor-α (TNFα), which is a well-known therapeutic target for rheumatoid arthritis and other autoimmune diseases. A protein library containing 677 proteins was used for the screen. Proteins with scores among the top 20% were further examined. Sixteen proteins from the top-ranking 67 proteins were selected for experimental study. Two of these proteins showed significant binding to TNFα in an in vitro binding study. The results of the present study demonstrate the power and potential application of protein-protein docking for the discovery of novel binding proteins for specific protein targets.
24732351 Curcumol suppresses RANKL-induced osteoclast formation by attenuating the JNK signaling pa 2014 May 2 Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases.
24578833 Is Certolizumab Pegol Safe and Effective in the Treatment of Patients with Moderate to Sev 2013 Aug BACKGROUND: Tumor necrosis factor-α (TNF-α) antibodies are currently used in patients with moderate to severe Crohn's disease (CD) who are unresponsive to conventional therapies. Certolizumab pegol (Cp) is one of the anti-TNF-α agents introduced for the management of CD and rheumatoid arthritis. OBJECTIVES: The aim of this meta-analysis is to assess the efficacy of Cp in inducing clinical response and remission in CD and the associated adverse events. The effect of Cp in terms of CD patients' C-reactive protein (CRP) level was also studied. PATIENTS AND METHODS: Literature was searched for studies investigated the efficacy of Cp on inducing clinical response and maintaining remission in the patients with CD between 1966 and July 2012. RESULTS: Among 165 potentially relevant studies, six with a total of 1695 patients met the inclusion criteria and were meta-analyzed. In comparison to control groups, patients who received Cp had a relative risk (RR) of 1.38 with absolute risk reduction (ARR) = 0.12; 95% CI = 0.03 to 0.21), number needed for treatment (NNT) = 9; P < 0.0001 ) for clinical response and RR of 1.54 (ARR = 0.09; 95% CI = -0.0198 to 0.2), (NNT = 12; P < 0.0001) for maintenance of clinical remission and non-significant RR of 1.24 (P = 0.052) for induction of clinical remission. Baseline CRP did not significantly alter the magnitude or response. Adverse events were not significantly different among patients receiving Cp comparing to placebo. CONCLUSIONS: Cp is effective for inducing clinical response and maintenance of clinical remission in patients with moderate to severe CD with similar side-effect profile as the control arms.
24566615 Immunosuppressive agent leflunomide: a SWNTs-immobilized dihydroortate dehydrogenase inhib 2014 Jun 2 Leflunomide [HWA 486 or RS-34821, 5-methyl-N-(4trifluoromethylphenyl)-4-isoxazole carboximide] is an immunosuppressive agent effective in the treatment of rheumatoid arthritis. Dihydroortate dehydrogenase (DHODH, EC 1.3.3.1) immobilization on the nanotubes was carried out and biochemical characterization of free and immobilized enzyme was determined. In comparison with free enzyme, the immobilized DHODH showed improved stability and reusability for investigation of inhibition pattern of drugs such as leflunomide. The experimental data showed that, DHODH was inhibited by the active metabolite of leflunomide (RS-61980) with a Ki and KI of 0.82 and 0.06 mM, respectively. Results exhibited mixed-type inhibition kinetics towards dihydroorotate as a substrate in the free and immobilized enzyme. Furthermore, the behavior of anticancer drug leflunomide adsorbed on the external surface of zigzag single walled (6,0) carbon and boron nitride nanotubes (SWCNT and SWBNNT) was studied by means of DFT calculations at the B3LYP/6-31G(*) level of theory. The larger adsorption energies and charges transfer showed that the adsorption of leflunomide onto SWBNNT is more stable than that the adsorption of leflunomide onto SWCNT. Frontier molecular orbitals (HOMO and LUMO) suggest that adsorption of leflunomide onto SWBNNT behave as charge transfer compounds with leflunomide as an electron donor and SWBNNT as an electron acceptor. Thus, nanotubes (NTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic application. The AIM theory has been also applied to analyze the properties of the bond critical points: their electron densities and their laplacians. Also, the natural bond orbital (NBO) calculations were performed to derive natural atomic orbital occupancies, and partial charges of the interacting atoms in the equilibrium tube-molecule distance.
24508770 Perceptions of dry eye disease management in current clinical practice. 2014 Mar OBJECTIVE: To assess the perceptions of eye care providers regarding the clinical management of dry eye. METHODS: Invitations to complete a 17-question online survey were mailed to 400 members of the North Carolina Ophthalmology and Optometry Associations including community optometrists, comprehensive ophthalmologists, and cornea specialists. RESULTS: The survey was completed by 100 eye care providers (25% response rate). Providers reported burning (46.5%) as the most frequent symptom described by patients, followed by foreign body sensation (30.3%) and tearing (17.2%). Most respondents (80.8%) listed artificial tears as the recommended first-line treatment, even though providers reported high failure rates for both artificial tears and cyclosporine A (Restasis). Rheumatoid arthritis, Sjögren syndrome, affective disorders such as anxiety and depression, history of photorefractive surgery, smoking, and thyroid disease were acknowledged as common comorbid conditions. CONCLUSIONS: The survey provided an informative snapshot into the preferences of eye care providers concerning the diagnosis and management of dry eye disease. Overall, burning was the most common symptom reported by patients. Providers relied more on patient history in guiding their clinical decisions than objective signs. The survey underscores the incongruence when comparing subjective symptoms with objective signs, thereby highlighting the urgent need for the development of reliable metrics to better quantify dry eye symptoms and also the development of a more sensitive and specific test that can be used as the gold standard to diagnose dry eye.
24361716 Glycosylation of a disintegrin and metalloprotease 17 affects its activity and inhibition. 2014 Mar 15 ADAM17 (a disintegrin and metalloprotease 17) is believed to be a tractable target in various diseases, including cancer and rheumatoid arthritis; however, it is not known whether glycosylation of ADAM17 expressed in healthy cells differs from that found in diseased tissue and, if so, whether glycosylation affects inhibitor binding. We expressed human ADAM17 in mammalian and insect cells and compared their glycosylation, substrate kinetics, and inhibition profiles. We found that ADAM17 expressed in mammalian cells was more heavily glycosylated than its insect-expressed analog. To determine whether differential glycosylation modulates enzymatic activity, we performed kinetic studies with both ADAM17 analogs and various TNFα-based substrates. The mammalian form of ADAM17 exhibited 10- to 30-fold lower kcat values than the insect analog, while the KM was unaffected, suggesting that glycosylation of ADAM17 can potentially play a role in regulating enzyme activity in vivo. Finally, we tested ADAM17 forms for inhibition by several well-characterized inhibitors. Active-site zinc-binding small molecules did not exhibit differences between the two ADAM17 analogs, while a non-zinc-binding exosite inhibitor of ADAM17 showed significantly lower potency toward the mammalian-expressed analog. These results suggest that glycosylation of ADAM17 can affect cell signaling in disease and might provide opportunities for therapeutic intervention using exosite inhibitors.
24325119 [Levels of acute-phase-reactants in patient with dermatomysitis and its correlations with 2013 Sep OBJECTIVE: To determine the association between acute-phase-reactants (APR) and interleukin-6 (IL-6) in patient with dermatomysitis (DM). METHODS: The levels of C-reactive protein (CRP), serum amyloid A protein(SAA) and serum ferritin (SF) in peripheral blood of 31 adult DM patients were determined by chemiluminescence immunoassay, and compared with those of 23 patients with systemic lupus erythematosus (SLE), 22 patients with rheumatoid arthritis (RA), and 18 patients with Sjagren syndrome (SS). The correlations between the levels of those APR and IL-6 were examined. We also measured dermatomyositis disease activity using myositis disease activity assessment tool (MDAAT), and examined its association with APR levels. RESULTS: DM patients had significantly lower level of CRP [(17. 08 +/- 17. 18) mg/L] than those patients with RA [(85. 95 +/-60.62) mg/L, P<0. 000 1], SLE [(51. 34+/-52. 98) mg/L, P=0. 006] and SS [(47. 00+/-47. 24) mg/L, P= 0.018]. DM patients had significantly lower level of SAA [(92. 04 +/- 98. 93) mg/L] than those patients with RA [(311.30 +/- 292. 45) mg/L, P= 0. 002] and SS [(284. 31 +/- 325. 30) mg/L, P= 0. 025]. DM patients had significantly higher level of SF [(510. 10 +/- 610. 73) ng/mL] than those patients with SS [(220. 33 +/- 164. 07) ng/ mL, P=0. 02], as well as those with RA and SLE albeit without statistical significance. All of the three APRs were positive correlated with IL-6 level. No significant associations between APR and systemic or global disease activities were found, although CRP was associated with constitutional disease activity and SF was associated with pulmonary disease activity. CONCLUSION: DM patients have lower levels of elevated APR than the other three common connective tissue diseases, which is associated with IL-6 but not with global disease activity.
23816245 Leflunomide suppresses growth in human medullary thyroid cancer cells. 2013 Nov BACKGROUND: Medullary thyroid cancer (MTC) is a neuroendocrine tumor that arises from the calcitonin-secreting parafollicular cells of the thyroid gland. Leflunomide (LFN) is a disease-modifying antirheumatic drug approved for the treatment of rheumatoid arthritis, and its active metabolite teriflunomide has been identified as a potential anticancer drug. In this study we investigated the ability of LFN to similarly act as an anticancer drug by examining the effects of LFN treatment on MTC cells. METHODS: Human MTC-TT cells were treated with LFN (25-150 μmol/L) and Western blotting was performed to measure levels of neuroendocrine markers. MTT assays were used to assess the effect of LFN treatment on cellular proliferation. RESULTS: LFN treatment downregulated neuroendocrine markers ASCL1 and chromogranin A. Importantly, LFN significantly inhibited the growth of MTC cells in a dose-dependent manner. CONCLUSIONS: Treatment with LFN decreased neuroendocrine tumor marker expression and reduced the cell proliferation in MTC cells. As the safety of LFN in human beings is well established, a clinical trial using this drug to treat patients with advanced MTC may be warranted.
23785733 Al(18)F-1,4,7-Triazacyclononane,1-glutaric acid-4,7-acetic acid-Glu-[cyclo(Arg-Gly-Asp-d-P 2004 Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell–cell and cell–matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. The α(v)β(3) integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of the α(v)β(3) integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. Antagonists of α(v)β(3) are being studied as antitumor and antiangiogenic agents, and the agonists of α(v)β(3) are being studied as angiogenic agents for coronary angiogenesis (6, 8, 9). Extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) contain a tripeptide sequence consisting of Arg-Gly-Asp (RGD), which binds to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for use with the imaging of tumors and tumor angiogenesis (10). Most cyclic RGD peptides are composed of five amino acids. Haubner et al. (11) reported that various cyclic RGD (c(RGD)) peptides exhibit selective inhibition of binding to α(v)β(3) (inhibition concentration (IC(50)), 7–40 nM) but not to integrins α(v)β(5) (IC(50), 600–4,000 nM) or α(IIb)β(3) (IC(50), 700–5,000 nM). Various radiolabeled c(RGD) peptides have been found to have high accumulation in tumors in nude mice (12). Dijkgraaf et al. (13) reported the evaluation of Al(18)F-1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid-Glu-[cyclo(Arg-Gly-Asp-d-Phe-Lys)](2) (Al(18)F-NODAGA-E-[c(RGDfK)](2)) for use with positron emission tomography (PET) imaging of α(v)β(3) in tumors.
23729444 GILZ overexpression inhibits endothelial cell adhesive function through regulation of NF-Π2013 Jul 1 Glucocorticoid-induced leucine zipper (GILZ) is an anti-inflammatory protein first identified in T lymphocytes. We recently observed that GILZ is highly expressed in synovial endothelial cells in rheumatoid arthritis. However, the function of GILZ in endothelial cells is unknown. To investigate the actions of GILZ in this cell type, we induced GILZ expression in HUVECs via transient transfection. GILZ overexpression significantly reduced the capacity of TNF-stimulated HUVECs to support leukocyte rolling, adhesion, and transmigration. These effects were associated with decreased expression of E-selectin, ICAM-1, CCL2, CXCL8, and IL-6. Experiments in a human microvascular endothelial cell line demonstrated that TNF-inducible NF-κB activity was significantly inhibited by overexpression of GILZ. Exogenous GILZ inhibited TNF-induced NF-κB p65 DNA binding, although this occurred in the absence of an effect on p65 nuclear translocation, indicating that the mechanism of action of exogenous GILZ in endothelial cells differs from that reported in other cell types. GILZ overexpression also inhibited TNF-induced activation of p38, ERK, and JNK MAPKs, as well as increased expression of the MAPK inhibitory phosphatase, MKP-1. In contrast, silencing endogenous GILZ in glucocorticoid-treated HUVECs did not alter their capacity to support leukocyte interactions. These data demonstrate that exogenous GILZ exerts inhibitory effects on endothelial cell adhesive function via a novel pathway involving modulation of NF-κB p65 DNA binding and MAPK activity. Induction of GILZ expression in endothelial cells may represent a novel therapeutic modality with the potential to inhibit inflammatory leukocyte recruitment.
23617140 [Effect of preoperative donation of autologous blood on venous thromboembolism disease aft 2013 Jan OBJECTIVE: To evaluate the effect of preoperative donation of autologous bood on venous thromboembolism (VTE) after total hip arthroplasty (THA). METHODS: Between Jan. 2007 and March. 2010,912 consecutive patients who had THAs performed in Hosptal for Special Surgery were collected, excluded patients with thrombocytopenia or pre-exising bleeding diathesis and patients for whom epidural analgesia was not possible. Among them, there were 428 males and 484 females with an average age of (65.28 +/- 11.90) years (ranged from 24 to 93 years). Among them, 835 cases (91.3%) had osteoarthritis, 32 cases (3.6%) had osteonerrosis, 20 cases (2.3%) had dysplasia, 20 cases (2.2%) had rheumatoid arthritis, and 5 cases (0.6%) had other diagnoses. The surgeries were performed under hypotensive epidural anestheisa (mean arterial pressure between 45 to 55 mm Hg) and through a posterolateral approach, minimizing the duration of femoral vein obstruction and reducing the load of intramedullary content to the venous system by repeated pulsatile lavage and aspiration of the femoral canal. The lower extremity was in the neutral position while working on the acetabulum and flexed and internally rotated while working on the femur. Whenever possible,the lower extremity was extended to a neutral position to restore femoral venous flow. Patients received one bolus of unfractionated intravenous heparin (10 to 15 U/kg), 1 to 2 minutes before femoral canal preparation. All patients were followed up at least 3 months postoperatively. No patient was lost to followed-up. RESULTS: Seven hundreds and fifty-two patients donated autologous blood before THA, 160 did not donate autologoud blood. The incidence of clinical symoptomatic VTE was 1.3% (11/912). Among the 11 patients with clinical symoptomatic VTE, 5 donated blood pre-operation (0.66%, 5/752) and 6 did not donate pre-operation (3.8%, 6/160). The rate of VTE after THA between autologous blood donation and no blood donation was statistically significant (P = 0.021 < 0.05. The incidence of deep vein thrombosis was 0.8%(8/ 912). Three patients had a symptomatic of Pulmonary embolism. CONCLUSION: A significant decrease in the incidence of VTE is noted in those who had donated blood preoperatively compared with those who had not.
23523531 Characterization of the first K⁺ channel blockers from the venom of the Moroccan scorpio 2013 Dec 1 The availability of a large variety of specific blockers, which inhibit different K(+) currents, would help to elucidate their differences in physiological function. Short peptide toxins isolated from scorpion venoms are able to block voltage-dependent or Ca(2+)-activated K(+) channels. Here, we have studied the venom of the Moroccan scorpion Buthus occitanus Paris (BoP) in order to find new peptides, which could enlarge our structure-function relationship knowledge on the Kv1.3 blocker Kaliotoxin (KTX) that belongs to the α-KTx3.1 family. Indeed and since more a decade, KTX is widely used by international investigators because it exhibits a quite sharp specificity and a high-affinity for the Kv1.3 channel, which is not only a neuronal channel but also a therapeutic target for diverse autoimmune diseases such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. The BoP venom was first investigated using HPLC and MALDI-TOF/MS. Further, the HPLC fractions were screened by ELISA with antibodies raised against KTX. These antibodies recognized at least three components toxic in mice by intracerebroventricular injection. They were further pharmacologically characterized by competition using (125)I-KTX bound to its specific binding sites on rat brain synaptosomes. A single component (4161 Da) inhibited totally the (125)I-KTX binding and with high-affinity (IC50 = 0.1 nM), while the two other components poorly competed with (IC50 > 100 nM). These toxins were sequenced in full by Edman's degradation. The high-affinity ligand (BoPKTX) shares 86% sequence identity with KTX and was classified as toxin α-KTx3.17. The two others peptides (BoP1 and BoP2, 4093 Da and 4121 Da, respectively) only differ by a Lys/Arg mutation. Their amino acid sequences were related to Martentoxin, which has been characterized from the Chinese scorpion Buthus martenzi Karch and described as both a BKCa and Kv1.3 blocker. Accordingly, they belong to the α-KTx16 family.
23430105 Associations between adverse social position and bone mineral density in women aged 50 yea 2013 Sep We examined the independent contribution of income to low bone mineral density in women aged 50 years and older. A significant dose-response association was observed between low income and low (bone mineral density) BMD, which was not explained by clinical risk factors or osteoporotic treatment in the year prior. INTRODUCTION: The association between social disadvantage and osteoporosis is attracting increased attention; however, little is known of the role played by income. We examined associations between income and bone mineral density (BMD) in 51,327 women aged ≥50 years from Manitoba, Canada. METHODS: Low BMD was defined as a T-score ≥2.5SD (femoral neck or minimum) measured by dual energy X-ray absorptiometry (DXA) 1996-2001. Mean household income was extracted from Canada Census 2006 public use files and categorized into quintiles. Age, weight and height were recorded at time of DXA. Parental hip fracture was self-reported. Diagnosed comorbidities, including osteoporotic fracture and rheumatoid arthritis, were ascertained from hospital records and physician billing claims. Chronic obstructive pulmonary disease was used as a proxy for smoking and alcohol abuse as a proxy for high alcohol intake. Corticosteroid use was obtained from the comprehensive provincial pharmacy system. Logistic regression was used to assess relationships between income (highest income quintile held as referent) and BMD, accounting for clinical risk factors. RESULTS: Compared to quintile 5, the adjusted odds ratio (OR) for low BMD at femoral neck for quintiles 1 through 4 were, respectively, OR1.41 (95%CI 1.29-1.55), OR1.32 (95%CI 1.20-1.45), OR1.19 (95%CI 1.08-1.30) and OR1.10 (95%CI 1.00-1.21). Similar associations were observed when further adjustment was made for osteoporotic drug treatment 12 months prior and when low BMD was defined by minimum T-score. CONCLUSIONS: Lower income was associated with lower BMD, independent of clinical risk factors. Further work should examine whether lower income increases the likelihood of treatment qualification.
23385979 T-cell immunoglobulin- and mucin-domain-containing molecule 3 genetic variants and HIV+ no 2013 Aug T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in inflammatory diseases such as rheumatoid arthritis, hepatitis B and C, and human immunodeficiency virus (HIV)-related inflammation. Recent studies have shown that chronic inflammation may greatly affect the pathogenesis of non-Hodgkin lymphomas (NHL). The aim of this study was to investigate whether polymorphisms in the TIM-3 gene were associated with susceptibility to non-NHL and HIV-related NHL. Three polymorphisms in TIM-3 gene (-1516G/T, -574G/T, and +4259T/G) were identified by polymerase chain reaction-restriction fragment length polymorphism in 434 NHL patients, 62 HIV-related NHL cases, and 512 healthy controls. Results showed that the prevalence of -574GT genotype and +4259TG genotype were significantly increased in the NHL cases than in controls (odds ratio (OR) = 2.72, 95% confidence interval (CI) = 1.50-4.92, p = 0.0006 and OR = 2.59, 95% CI = 1.49-4.49, p = 0.0005, respectively). The -1516G/T polymorphism did not reveal significant difference between patients and healthy controls. When analyzing the TIM-3 polymorphisms in HIV-related NHL patients, data showed that HIV+ NHL patients had higher prevalence of -574GT or +4259TG genotypes than those cases without HIV infection (OR = 3.48, 95% CI = 1.67-7.28, p = 0.0005 and OR = 2.92, 95% CI = 1.42-6.01, p = 0.0026, respectively). These results suggested polymorphisms in TIM-3 gene could be new risk factors for NHL as well as HIV-related NHL and suggested a possible role of the inflammatory factor in these diseases.