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ID PMID Title PublicationDate abstract
27777916 Result of Modular Necks in Primary Total Hip Arthroplasty with a Average Follow-up of Four 2016 Sep PURPOSE: This study aimed to investigate the outcomes of modular neck-utilization in primary total hip arthroplasty (THA). MATERIALS AND METHODS: Thirty patients (34 hips) who had modular stem THA between April 2011 and January 2013 were evaluated. There were 19 men and 11 women with a mean age of 61.2 years at the time of surgery. There were 20 cases of osteonecrosis of femoral head, 7 cases of osteoarthritis, 6 cases of femur neck fracture, and 1 case of rheumatoid arthritis. No patients presented with anatomical deformity of hip. Patients were operated on using a modified Watson-Jones anterolateral approach. All patients underwent clinical and radiological follow-up at 6 weeks, 3, 6, and 12 months, and every year postoperatively. The mean duration of follow-up was 48.2 months (range, 39 to 59 months). RESULTS: The average Harris hip score improved from 63.7 to 88.1 at the final follow-up. Radiographically, mean acetabular cup inclination was 45.3°(range, 36°-61°) and anteversion was 21.7°(range, 11°-29°). All were neutral-positioned stems except 5 which were varus-positioned stems. In only 3 cases (8.8%), varus or valgus necks were required. A case of linear femoral fracture occurred intraoperatively and 1 case of dislocation occurred at postoperative 2 weeks. No complications at modular junction were occurred. CONCLUSION: Our study shows that the use of modular necks had favorable clinical and radiographic results. This suggests that the use of modular neck in primary THA without anatomical deformity is safe at a follow-up of 39 months.
27658265 Localization, Shedding, Regulation and Function of Aminopeptidase N/CD13 on Fibroblast lik 2016 Aminopeptidase N/CD13 is highly expressed by fibroblast like synoviocytes (FLS) and may play a role in rheumatoid arthritis (RA). CD13 was previously detected in human synovial fluid where it was significantly increased in RA compared to osteoarthritis. In this study we found that CD13 in biological fluids (plasma, synovial fluid, FLS culture supernatant) is present as both a soluble molecule and on extracellular vesicles, including exosomes, as assessed by differential ultracentrifugation and density gradient separation. Having determined CD13 could be released as a soluble molecule from FLS, we examined potential mechanisms by which CD13 might be shed from the FLS membrane. The use of protease inhibitors revealed that CD13 is cleaved from the FLS surface by metalloproteinases. siRNA treatment of FLS revealed one of those proteases to be MMP14. We determined that pro-inflammatory cytokines (TNFα, IFNγ, IL-17) upregulated CD13 mRNA in FLS, which may contribute to the increased CD13 in RA synovium and synovial fluid. Inhibition of CD13 function by either inhibitors of enzymatic activity or anti-CD13 antibodies resulted in decreased growth and diminished migration of FLS. This suggests that CD13 may be involved in the pathogenic hyperplasia of RA FLS. This data expands potential roles for CD13 in the pathogenesis of RA.
27644575 Clinical features and outcome of acute exacerbation of interstitial pneumonia associated w 2016 Acute exacerbation (AE) of interstitial lung disease is reported to be developed in not only idiopathic pulmonary fibrosis but also connective tissue disease-associated interstitial pneumonia (CTD-IP). As the significance of AE of CTD-IP has not been so widely recognized, its clinical feature is not fully elucidated. In the present study, we investigated the incidence, clinical features and outcome of AE of CTD-IP. We retrospectively reviewed admitted cases in our department with medical record from 2011 to 2015. Among 155 patients with CTD-IP, 10 (6.5%) cases developed AE (6 rheumatoid arthritis, 2 polymyositis/dermatomyositis, 1 systemic lupus erythematosus, 1 Sjögren syndrome), and one died of AE within 30 days. Median survival time after the onset of AE was 169 days in all 10 patients. The treatment with immunosuppressant just before AE onset might improve the prognosis of AE. The median survival time after the onset of AE was significantly longer in patients showing good response to corticosteroid compared with those with poor response to corticosteroid (805 days and 45 days, respectively) (p <0.05), suggesting that there are some cases in CTD-IP, showing the good response to corticosteroid even when AE was complicated. J. Med. Invest. 63: 294-299, August, 2016.
27629281 RORγ antagonists and inverse agonists: a patent review. 2017 Jan The transcription factor RORγ plays a critical role in the expression of pro-inflammatory cytokine interleukin IL-17 and is therefore an attractive target for the treatment of inflammatory diseases. Interest in this molecular target has been heightened by the advancement of orally and topically administered RORγ modulators into clinical trials. Areas covered: The present review seeks to summarize published patent applications from assignee companies that have disclosed Investigational New Drug (IND) filings for small molecule RORγ/RORγt antagonists and inverse agonists. Expert opinion: The field of RORγ research is extremely competitive, with the majority of companies targeting psoriasis as the primary disease indication. Vitae Pharmaceuticals is currently the most advanced, with a potential first-in-class oral RORγ-modulator for the treatment of psoriasis. Future efforts will likely expand into potential applications of RORγ-modulators in the lesser explored immune-related areas of rheumatoid arthritis, type 1 diabetes, lupus, and irritable bowel disorder, as well as cancer immunotherapy and castration-resistant prostate cancer.
27580425 Differences in expression of Wnt antagonist Dkk1 in healthy versus pathological bone sampl 2017 Jan Wnt/β-catenin signalling components was shown to affect bone cells function including chondrocytes.Secreted Dkk1, a potent osteogenesis inhibiting factor mediates bone loss in diseased bones by suppressing the biological actions of Wnt proteins. In addition, increased Dkk1 signalling inhibits chondrogenesis in new bone formation. Recent findings also show there exists a cross-talk between the chondrocytes and the cells of the osteoblast lineage, which are the most affected cell types in muskuloskeletal disorders. This study investigated whether spatial expression of Dkk1 is confined to only osteoblasts, osteocytes or chondrocytes. The second objective was to detect a difference in the Dkk1 expression pattern in healthy subjects when compared to pathological state. To elucidate the cell specificity of Dickkopf-1 (Dkk1) in healthy bones, samples from female Sprague-Dawley rats were tested against two different antibodies with the two most widely accepted visualization system (ABC and Envision). The findings show Dkk1 specificity predominantly for osteoblasts, chondrocytes and osteocytes depending upon the antibody used. In addition, Dkk1 expression was evaluated in different cells of human osteoarthritis (OA) and rheumatoid arthritis (OA) patients. Its overexpression in pathologic state also suggests the role of Dkk1 in bone formation. This is scientifically and clinically important in studying the effect of Dkk1 in bone healing and in designing treatments for patients with compromised bone status. Taking into consideration the paradigm that cartilage and subchondral bone behave as an interconnected functional unit, normalization of cell behaviour in one compartment may have benefits in both tissues.
27502541 Discovery of Imidazoquinolines as a Novel Class of Potent, Selective, and in Vivo Efficaci 2016 Aug 25 Cancer Osaka thyroid (COT) kinase is an important regulator of pro-inflammatory cytokines in macrophages. Thus, pharmacologic inhibition of COT should be a valid approach to therapeutically intervene in the pathogenesis of macrophage-driven inflammatory diseases such as rheumatoid arthritis. We report the discovery and chemical optimization of a novel series of COT kinase inhibitors, with unprecedented nanomolar potency for the inhibition of TNFα. Pharmacological profiling in vivo revealed a high metabolism of these compounds in rats which was demonstrated to be predominantly attributed to aldehyde oxidase. Due to the very low activity of hepatic AO in the dog, the selected candidate 32 displayed significant blood exposure in dogs which resulted in a clear prevention of inflammation-driven lameness. Taken together, the described compounds both potently and selectively inhibit COT kinase in primary human cells and ameliorate inflammatory pathologies in vivo, supporting the notion that COT is an appropriate therapeutic target for inflammatory diseases.
27306611 Martingale residual-based method to control for confounders measured only in a validation 2016 Nov 10 Unmeasured confounding remains an important problem in observational studies, including pharmacoepidemiological studies of large administrative databases. Several recently developed methods utilize smaller validation samples, with information on additional confounders, to control for confounders unmeasured in the main, larger database. However, up-to-date applications of these methods to survival analyses seem to be limited to propensity score calibration, which relies on a strong surrogacy assumption. We propose a new method, specifically designed for time-to-event analyses, which uses martingale residuals, in addition to measured covariates, to enhance imputation of the unmeasured confounders in the main database. The method is applicable for analyses with both time-invariant data and time-varying exposure/confounders. In simulations, our method consistently eliminated bias because of unmeasured confounding, regardless of surrogacy violation and other relevant design parameters, and almost always yielded lower mean squared errors than other methods applicable for survival analyses, outperforming propensity score calibration in several scenarios. We apply the method to a real-life pharmacoepidemiological database study of the association between glucocorticoid therapy and risk of type II diabetes mellitus in patients with rheumatoid arthritis, with additional potential confounders available in an external validation sample. Compared with conventional analyses, which adjust only for confounders measured in the main database, our estimates suggest a considerably weaker association. Copyright © 2016 John Wiley & Sons, Ltd.
27231550 A comparison of the direct medical costs for individuals with or without basal or squamous 2016 OBJECTIVES: The composition of the medical costs incurred by people treated for basal cell and squamous cell carcinomas (hereafter keratinocyte cancers) is not adequately understood. We sought to compare the medical costs of individuals with or without keratinocyte cancers. METHODS: We used national health insurance data to analyze the direct medical costs of 2000 cases and 2000 controls nested within the QSkin prospective cohort study (n = 43,794) conducted in Australia. We reconstructed the medical history of patients using medical and pharmaceutical item codes and then compared the health service costs of individuals treated for keratinocyte cancers with those not treated for keratinocyte cancers. RESULTS: Individuals treated for keratinocyte cancers consumed on average AUD$1320 per annum more in medical services than those without keratinocyte cancers. Only 23.2% of costs were attributed to the explicit treatment of keratinocyte cancers. The principal drivers of the residual costs were medical attendances, surgical procedures on the skin, and histopathology services. We found significant positive associations between history of treatment for keratinocyte cancers with treatments for other health conditions, including melanoma, cardiovascular disease, lipidemia, osteoporosis, rheumatoid arthritis, colorectal cancer, prostate cancer, and tuberculosis. CONCLUSION: Individuals treated for keratinocyte cancers have substantially higher medical costs overall than individuals without keratinocyte cancers. The direct costs of skin cancer excision account for only one-fifth of this difference.
27224044 The Pharmacological Effects and Mechanism of Tripterygium wilfordii Hook F in Central Nerv 2016 Jul OBJECTIVE: Extracts of the Chinese herb Tripterygium wilfordii Hook F (TwHF) have potent anti-inflammatory functions and are widely used to treat rheumatoid arthritis and Crohn's disease. They have also been considered as potential drugs in the treatment of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. METHODS: A systematic search of MEDLINE, EMBASE, PubMed, and the China National Knowledge Infrastructure (CNKI) was performed. We reviewed many Chinese- and English-language articles. RESULTS: Recent studies have indicated that TwHF extracts, such as triptolide and tripchlorolide, are able to attenuate progression of this neuroimmunologic disorder because of their immunoregulatory, neurotrophic, and neuroprotective effects, but use of these extracts is often accompanied by acute and chronic toxicity. CONCLUSIONS: This review systematically summarizes the effects, safety consideration, and molecular mechanisms of action of TwHF extracts with regard to their inhibition of microglia activation, T cell functions, and transcriptional activation of nuclear factor (NF)-κB signaling.
27186376 Diagnosis of perinuclear anti-neutrophil cytoplasmic antibody-associated microscopic polya 2016 BACKGROUND: An association between silica exposure and autoimmune diseases including rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis has been made. CASE PRESENTATION: A 56-year-old male presented with silicosis and had an occupational history of precious metal processing for 30 years and a 30 pack-year smoking history. The patient was diagnosed with pneumoconiosis and received compensation. No other complications were reported for pneumoconiosis. The patient suddenly presented with a non-specific headache for several days and microscopic hematuria was identified upon examination in the outpatient clinic. Following several weeks, the patient presented with aggravated dyspnea and hemoptysis, and his Modification of Diet in Renal Disease estimated glomerular filtration rate indicated acute kidney injury. Diagnostic analysis revealed perinuclear ANCA-associated microscopic polyangiitis (p-ANCA-associated MPA). CONCLUSION: Exposure to silica dust was likely one of the cause of p-ANCA-associated MPA. Possible pathogenic mechanisms of autoimmune diseases in silicotics and emphasis of the necessity for early diagnosis are discussed.
27055155 Abatacept Treatment Does Not Preserve Renal Function in the Streptozocin-Induced Model of 2016 Diabetic nephropathy (DN) is one of the most severe complications of diabetes and remains the largest cause of end-stage renal disease in the Western world. Treatment options are limited and novel therapies that effectively slow disease progression are warranted. Previous work suggested that treatment with CTLA4-Ig (abatacept), a molecule that binds and blocks B7-1 and is licensed for the treatment of rheumatoid arthritis, could ameliorate DN. This study was designed to assess whether B7-1 signalling constitutes a promising therapeutic pathway for DN. Mice injected with streptozotocin (STZ) were treated with abatacept and glycemia and renal function were assessed. No differences were found in diabetes progression, albumin excretion rates or albumin/creatine ratios, while mesangial expansion was unaltered at endpoint. Except for increased renal CCL5, treatment did not affect a panel of gene expression endpoints reflecting early fibrotic changes, inflammation and kidney injury. Finally, abatacept treatment effectively reduced the accumulation of activated CD4+ T cells in the kidney, suggesting that renal T cell inflammation is not a driving factor in the pathology of the STZ model. In conjunction with the recent data discounting the expression of B7-1 on podocytes, our present data do not support a role for abatacept in DN treatment.
26955178 Subcutaneous versus intraarticular closed suction indwelling drainage after total knee art 2016 Jan BACKGROUND: Total knee arthroplasty (TKA) is widely accepted treatment for moderate or severe osteoarthritis and rheumatoid arthritis. Significant blood loss can be seen during the early postoperative period where a blood transfusion may be necessary. Closed suction drainage is known to prevent the formation of hematomas in the operative field, decrease tension on incisions, diminish delayed wound healing and reduce the risk of infection. Subcutaneous indwelling closed suction drainage method has been known to be beneficial and an alternative to the intraarticular indwelling method. This prospective randomized study was to compare the visible, hidden, total blood loss and postoperative hemodynamic change of subcutaneous and intraarticular indwelling closed suction drainage method after TKA. MATERIALS AND METHODS: One hundred and sixty patients with primary osteoarthritis who underwent unilateral TKA were enrolled; group A with subcutaneous (n = 78) and group B with intraarticular (n = 79) indwelling closed suction drainage method. Total blood loss, visible blood loss, internal blood loss, postoperative day 1, 5(th), 10(th) day hemoglobin, hematocrit levels were compared. Allogeneic blood transfusion rate and complications related to soft tissue hematoma formation were additionally compared. RESULTS: Allogenic transfusion requirements between subcutaneous drainage group and intraarticular drainage groups (6.4% vs. 24.1%) were significantly different (P = 0.002). Although the minor complications such as the incidence of bullae formation and the ecchymosis were higher in the subcutaneous indwelling group, the functional outcome at postoperative 2 year did not demonstrate the difference from intraarticular drainage group. CONCLUSION: Subcutaneous indwelling closed suction drainage method is a reasonable option after TKA for reduction of postoperative bleeding and transfusion rate.
26907852 TWEAK/Fn14 signaling: a promising target in intervertebral disc degeneration. 2016 Sep Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent chemoattractant cytokine with various biological functions, such as stimulation of angiogenesis, induction of proinflammatory cytokines, regulation of cellular proliferation and apoptosis. Therefore, it has also been implicated in several pathological processes, from cancer to inflammatory diseases. Remarkably, TWEAK and its receptors, fibroblast growth factor inducible 14 (Fn14), are also present in intervertebral disc (IVD) tissue, where they play a role in the pathogenesis of IVD degeneration. The interaction of TWEAK with Fn14 is involved in physiological and pathological activities of IVD degeneration patients, which includes apoptosis of endplate chondrocytes, extracellular matrix degradation, reduction in proteoglycan synthesis and so on. The blockade of this interaction results in suppressing over-production of proinflammatory factors and cell death in in vivo or in vitro experiments, suggesting that TWEAK/Fn14 signaling may be therapeutically relevant in IVD degeneration, and the targeting of TWEAK or Fn14 has been proposed as a potential therapeutic approach for autoimmune diseases such as Rheumatoid arthritis (RA). In this article, we discuss the biological features of TWEAK/Fn14 signaling and summarize recent advances in our understanding of the role of TWEAK/Fn14 signaling in the pathogenesis and treatment of IVD degeneration. We think that the blockade of TWEAK/Fn14 signaling may be a promising therapeutic strategy for IVD degeneration in the near future.
26859242 General false positive ELISA reactions in visceral leishmaniasis. Implications for the use 2016 Apr Leishmaniasis is a neglected disease in tropical countries. Clinical and laboratory features may mimic autoimmune diseases and this can complicate the Leishmania diagnosis. Due to our previous investigation for false anti-CCP2 reactivity in Leishmania-infected subjects and our interest in immunity against the joint-specific collagen type II (CII) in rheumatoid arthritis (RA) we investigated the same cohort for anti-CII antibodies. We found elevated anti-CII reactivity in Leishmania-infected patients as compared to controls. When anti-CII OD values were compared with BSA-blocked control plates we found higher reactivity against BSA than in CII-coated plates in many Leishmania-infected patients. The percentage of such false positive anti-CII reactions increased with inflammatory activity, and was found in almost all Leishmania patients with highly active inflammatory disease, but was as low in Sudanese healthy controls as well as among Swedish RA patients. The correlation coefficients between false positive anti-CII and anti-CCP2 measured with a commercial ELISA were highest for patients with the most inflammatory disease but non-significant for Sudanese controls and Swedish RA patients, arguing that our findings may have general implications for ELISA measurements in leishmaniasis. ELISA investigations in areas endemic for leishmaniasis might benefit from individual-specific control wells for each serum sample. This approach might also be applicable to other geographical areas or patient groups with high incidence of inflammatory and infectious diseases.
26729890 AMSSM scientific statement concerning viscosupplementation injections for knee osteoarthri 2016 Jan Osteoarthritis (OA) is a disabling disease that produces severe morbidity reducing physical activity. Our position statement on treatment of knee OA with viscosupplementation injection (hyaluronic acid, HA) versus steroid (intra-articular corticosteroids, IAS) and placebo (intra-articular placebo, IAP) is based on the evaluation of treatment effect by examining the number of participants within a treatment arm who met the Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria, which is different and more relevant than methods used in other reviews which examined if the average change across the treatment groups were clinically different. We performed a systematic literature search for all relevant articles from 1960 to August 2014 in the MEDLINE, EMBASE and Cochrane CENTRAL. We performed a network meta-analysis (NMA) of the relevant literature to determine if there is a benefit from HA as compared with IAS and IAP. 11 papers met the inclusion criteria from the search strategy. On NMA, those participants receiving HA were 15% and 11% more likely to respond to treatment by OMERACT-OARSI criteria than those receiving IAS or IAP, respectively (p<0.05 for both). In the light of the aforementioned results of our NMA, the American Medical Society for Sport Medicine recommends the use of HA for the appropriate patients with knee OA.
26584734 Methylation of an intragenic alternative promoter regulates transcription of GARP. 2016 Feb Alternative promoter usage has been proposed as a mechanism regulating transcriptional and translational diversity in highly elaborated systems like the immune system in humans. Here, we report that transcription of human glycoprotein A repetitions predominant (GARP) in regulatory CD4 T cells (Tregs) is tightly regulated by two alternative promoters. An intragenic promoter contains several CpGs and acts as a weak promoter that is demethylated and initiates transcription Treg-specifically. The strong up-stream promoter containing a CpG-island is, in contrast, fully demethylated throughout tissues. Transcriptional activity of the strong promoter was surprisingly down-regulated upon demethylation of the weak promoter. This demethylation-induced transcriptional attenuation regulated the magnitude of GARP expression and correlated with disease activity in rheumatoid arthritis. Treg-specific GARP transcription was initiated by synergistic interaction of forkhead box protein 3 (Foxp3) with nuclear factor of activated T cells (NFAT) and was underpinned by permissive chromatin remodeling caused by release of the H3K4 demethylase, PLU-1. Our findings describe a novel function of alternative promoters in regulating the extent of transcription. Moreover, since GARP functions as a transporter of transforming growth factor β (TGFβ), a cytokine with broad pleiotropic traits, GARP transcriptional attenuation by alternative promoters might provide a mechanism regulating peripheral TGFβ to avoid unwanted harmful effects.
26477217 Financial Incentives, Workplace Wellness Program Participation, and Utilization of Health 2015 Aug This paper analyzes data from a large employer that enhanced financial incentives to encourage participation in its workplace wellness programs. It examines, first, the effect of financial incentives on wellness program participation, and second, it estimates the impact of wellness program participation on utilization of health care services and spending. The Patient Protection and Affordable Care Act of 2010 (PPACA) allows employers to provide financial incentives of as much as 30 percent of the total cost of coverage when tied to participation in a wellness program. Participation in health risk assessments (HRAs) increased by 50 percentage points among members of unions that bargained in the incentive, and increased 22 percentage points among non-union employees. Participation in the biometric screening program increased 55 percentage points when financial incentives were provided. Biometric screenings led to an average increase of 0.31 annual prescription drug fills, with related spending higher by $56 per member per year. Otherwise, no significant effects of participation in HRAs or biometric screenings on utilization of health care services and spending were found. The largest increase in medication utilization as a result of biometric screening was for statins, which are widely used to treat high cholesterol. This therapeutic class accounted for one-sixth of the overall increase in prescription drug utilization. Second were antidepressants, followed by ACE inhibitors (for hypertension), and thyroid hormones (for hypothyroidism). Biometric screening also led to significantly higher utilization of biologic response modifiers and immunosuppressants. These specialty medications are used to treat autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, and are relatively expensive compared with non-specialty medications. The added spending associated with the combined increase in fills of 0.02 was $27 per member per year--about one-half of the overall increase in prescription drug spending from those who participated in biometric screenings.
26457359 Novel glucocorticoids: where are we now and where do we want to go? 2015 Jul Glucocorticoid (GC) therapy is widely accepted as effective treatment for many inflammatory conditions. However, the potential of GC to produce adverse effects may prompt both patients and prescribing doctors to take a critical view on these important drugs. The increasing awareness of potential side effects suggests that the improvement of the benefit:risk ratio represents both a current need and an ongoing challenge. The developing and detailed knowledge on mechanisms of GC action has resulted in exploration of numerous approaches to optimise treatments with these important drugs. Most advanced is a chronotherapeutic formulation of prednisone (termed modified- or delayed-release prednisone) that has been recently approved in many European and other countries, and very recently also in the United States. Another interesting example is the development of selective GC receptor (GR) agonists, with clinical studies being currently underway. The development of so called liposomal GC is ongoing. However, another approach, the synergistic combination of prednisolone and dipyridamole, has been recently discontinued because a phase 2b study with the treatment in patients with rheumatoid arthritis showed a statistically significant improvement in disease activity score measured in 28 joints (DAS28) compared with placebo, but not compared with prednisolone alone. Other interesting developments and promising concepts include the development of nitrosteroids, targeting the membrane-bound GR and the use of extracts of the medicinal plant Tripterygium wilfordii Hook F.
26338477 Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss. 2015 Sep 4 The activity of protein kinases IKK-ε and TANK-binding kinase 1 (TBK1) has been shown to be associated with inflammatory diseases. As an inhibitor of IKK-ε and TBK1, amlexanox is an anti-inflammatory, anti-allergic, immunomodulator and used for treatment of ulcer, allergic rhinitis and asthma in clinic. We hypothesized that amlexanox may be used for treatment of osteoclast-related diseases which frequently associated with a low grade of systemic inflammation. In this study, we investigated the effects of amlexanox on RANKL-induced osteoclastogenesis in vitro and ovariectomy-mediated bone loss in vivo. In primary bone marrow derived macrophages (BMMs), amlexanox inhibited osteoclast formation and bone resorption. At the molecular level, amlexanox suppressed RANKL-induced activation of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPKs), c-Fos and NFATc1. Amlexanox decreased the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. Moreover, amlexanox enhanced osteoblast differentiation of BMSCs. In ovariectomized (OVX) mouse model, amlexanox prevented OVX-induced bone loss by suppressing osteoclast activity. Taken together, our results demonstrate that amlexanox suppresses osteoclastogenesis and prevents OVX-induced bone loss. Therefore, amlexanox may be considered as a new therapeutic candidate for osteoclast-related diseases, such as osteoporosis and rheumatoid arthritis.
26229389 Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome. 2015 Jul Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome.