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https://www.readbyqxmd.com/read/28448562/the-impact-of-anti-drug-antibodies-on-drug-concentrations-and-clinical-outcomes-in-rheumatoid-arthritis-patients-treated-with-adalimumab-etanercept-or-infliximab-results-from-a-multinational-real-world-clinical-practice-non-interventional-study
#1
Robert J Moots, Ricardo M Xavier, Chi Chiu Mok, Mahboob U Rahman, Wen-Chan Tsai, Mustafa H Al-Maini, Karel Pavelka, Ehab Mahgoub, Sameer Kotak, Joan Korth-Bradley, Ron Pedersen, Linda Mele, Qi Shen, Bonnie Vlahos
OBJECTIVE: To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes. METHODS: This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6-24 months with ETN, ADL, or IFX...
2017: PloS One
https://www.readbyqxmd.com/read/28448195/design-characteristics-of-the-corrona-japan-rheumatoid-arthritis-registry
#2
Hisashi Yamanaka, Mitsumasa Kishimoto, Dimitrios A Pappas, Jeffrey D Greenberg, Joel M Kremer, Yoshiya Tanaka
OBJECTIVES: The primary objective is to prospectively study the comparative safety and effectiveness of older and newer classes of nonbiologic DMARDs (Disease-modifying antirheumatic drugs), biologic DMARDs and targeted synthetic therapies approved for rheumatoid arthritis (RA) in a real-world patient population in Japan. METHODS: Prospective, multicenter, noninterventional, observational study across geographic distribution of both private and public institutions for patients with RA who are newly prescribed one of the following medications: (1) methotrexate; (2) anti-TNF biologic DMARDs; (3) non-TNF biologic DMARDs; and (4) approved JAK inhibitors at the time of enrollment into the registry...
April 27, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28447762/inhibition-of-aldose-reductase-ameliorates-ethanol%C3%A2-induced-steatosis-in-hepg2-cells
#3
Longxin Qiu, Chengchao Cai, Xiangqian Zhao, Yan Fang, Weibiao Tang, Chang Guo
Aldose reductase (AR) expression is increased in liver tissue of patients with ethanol‑induced liver disease. However, the exact role of AR in the development of ethanol‑induced liver disease has yet to be elucidated. The present study aimed to determine the effect of an AR inhibitor on ethanol‑induced steatosis in HepG2 cells and to identify possible underlying molecular mechanisms. Steatosis was induced in HepG2 cells by stimulating cells with 100 mM absolute ethanol for 48 h. Oil Red O staining was used to detect the lipid droplet accumulation in cells...
March 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28446249/adipose-derived-mesenchymal-stem-cells-modulate-cd14-cd16-expression-on-monocytes-from-sepsis-patients-in-vitro-via-prostaglandin-e2
#4
Guanguan Qiu, Guoping Zheng, Menghua Ge, Lanfang Huang, Haijiang Tong, Ping Chen, Dengming Lai, Yaoqin Hu, Baoli Cheng, Qiang Shu, Jianguo Xu
BACKGROUND: Mesenchymal stem cells (MSCs) have been shown to reduce sepsis-induced inflammation and improve survival in mouse models of sepsis. CD16(+) monocytes are proinflammatory and abundant in inflammatory conditions such as sepsis. The primary objective in this exploratory study was to determine the effects of adipose-derived MSCs (ASCs) on three subsets of monocytes from sepsis patients in vitro and to delineate the underlying mechanism. METHODS: This is a prospective cohort study of patients admitted to the medical intensive care unit (ICU) at an academic medical center...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28446212/doctors-preferences-in-de-escalating-dmards-in-rheumatoid-arthritis-a-discrete-choice-experiment
#5
T Martijn Kuijper, Riëtte Folmer, Elly A Stolk, Johanna M W Hazes, Jolanda J Luime
BACKGROUND: Current guidelines suggest reduction of DMARDs can be considered in RA patients in remission. Objectives were (1) to estimate the relative importance of patient characteristics rheumatologists consider in their decision to de-escalate (2) to assess whether heterogeneity exists among rheumatologists with respect to de-escalation and (3) to identify the preferred de-escalation strategy. METHODS: A discrete choice experiment (DCE) was conducted. All rheumatologists and trainees in The Netherlands were invited to participate...
April 26, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28444889/invasive-fungal-infections-in-paediatric-patients-treated-with-macromolecular-immunomodulators-other-than-tumour-necrosis-alpha-inhibitors
#6
REVIEW
Ioannis Kyriakidis, Athanasios Tragiannidis, Ilse Zündorf, Andreas H Groll
An expanding list of immunomodulatory or immunosuppressive monoclonal antibodies (mAbs) and biologic therapeutics is currently entering clinical practice, particularly in the areas of oncology, transplantation and autoimmune disorders. These agents are directed against molecules or cells involved in inflammation and immunity and may therefore be associated with serious and opportunistic infections. The purpose of this review was to critically analyse the literature on invasive fungal infections (IFIs) occurring in association with mAbs and fusion proteins other than tumour necrosis alpha (TNF-α) inhibitors, including therapeutics modulating T-cell-mediated pathologies (muromonab, abatacept, belatacept, ipilimumab, basiliximab, daclizumab), inducing lymphopenia (alemtuzumab), depleting CD20+ B cells (rituximab) and interfering with various targets (anakinra, natalizumab, blodalumab, ixekizumab and others) with a focus on children, and to provide a framework of evaluating the risk for IFIs in this population...
April 26, 2017: Mycoses
https://www.readbyqxmd.com/read/28444734/highly-electronegative-low-density-lipoprotein-l5-evokes-microglial-activation-and-creates-a-neuroinflammatory-stress-via-toll-like-receptor-4-signaling
#7
Liang-En Yu, Chiou-Lian Lai, Ching-Tien Lee, Jiz-Yuh Wang
Atherogenic risk factors, such as hypercholesterolemia, are associated with increased risk of neurodegeneration, especially Alzheimer's dementia. Human plasma electronegative low-density lipoprotein [LDL(-)], especially L5, may serve as an important contributing factor. L5 promoting an inflammatory action in atherosclerosis has been extensively studied. However, the role of L5 in inducing neuroinflammation remains unknown. Here, we examined the impact of L5 on immune activation and cell viability in cultured BV-2 microglia...
April 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28442350/extracellular-nampt-visfatin-induces-proliferation-through-erk1-2-and-akt-and-inhibits-apoptosis-in-breast-cancer-cells
#8
Zafar Gholinejad, Nejat Kheiripour, Mitra Nourbakhsh, Davod Ilbeigi, Kiarash Behroozfar, Zahra Hesari, Abolfazl Golestani, Mohammad Shabani, Nahid Einollahi
BACKGROUND: Visfatin is a novel adipokine and proinflammatory cytokine which is implicated in breast cancer progression. The exact proliferative and anti-apoptotic mechanisms of visfatin are still under debate. In this study, the effect of extracellular visfatin on proliferation and apoptosis of breast cancer cells were investigated considering key regulatory molecules in these procedures. METHODS: BrdU (Bromodeoxyuridine) experiment was used to assess cell proliferation in response to visfatin treatment...
April 22, 2017: Peptides
https://www.readbyqxmd.com/read/28441960/incorporating-assessment-of-the-cervical-facet-joints-in-the-modified-stoke-ankylosing-spondylitis-spine-score-is-of-additional-value-in-the-evaluation-of-spinal-radiographic-outcome-in-ankylosing-spondylitis
#9
Fiona Maas, Suzanne Arends, Elisabeth Brouwer, Hendrika Bootsma, Reinhard Bos, Freke R Wink, Anneke Spoorenberg
BACKGROUND: To aim was to investigate the additional value of incorporating the de Vlam cervical facet joint score in the modified ankylosing spondylitis (AS) spine score (mSASSS) for the evaluation of spinal radiographic outcome in AS. METHOD: Baseline and 4-year radiographs from 98 consecutive patients from the Groningen Leeuwarden AS (GLAS) cohort, who had AS treated with TNF-α inhibitors, were scored by two readers; the vertebral bodies were assessed according to the mSASSS (0-72) and cervical facet joints (C2-C7) were assessed according to the method of de Vlam (0-15)...
April 26, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28440797/potential-mechanisms-of-microrna-141-3p-to-alleviate-chronic-inflammatory-pain-by-down-regulation-of-downstream-target-gene-hmgb1-in-vitro-and-in-vivo-studies
#10
W-S Shen, X-Q Xu, N-N Zhai, Z-S Zhou, J Shao, Y-H Yu
The present study aimed to investigate the potential role of microRNA-141-3p (miR-141-3p) in chronic inflammatory pain (CIP) by targeting HMGB1 gene. In the in vitro study, BV2 microglial cells were selected and assigned into blank, lipopolysaccharide (LPS), miR-141-3p mimics, mimics control, miR-141-3p inhibitor, inhibitor control, miR-141-3p mimics+LPS, mimics control+ LPS, miR-141-3p inhibitor+LPS, and inhibitor control+LPS groups. Ninety-six rats were randomly divided into 8 groups (12 rats in each group): blank control, model control, negative control (NC), miR-141-3p mimics+CFA, mimics control+CFA, HMGB1 shRNA+CFA, HMGB1 NC+CFA, and miR-141-3p mimics+HMGB1 shRNA+CFA groups...
April 25, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28440509/modulation-of-mmp-2-and-9-secretion-by-cytokines-inducers-and-inhibitors-in-human-melanoma-a-2058-cells
#11
M Waheed Roomi, Tatiana Kalinovsky, Aleksandra Niedzwiecki, Matthias Rath
Melanoma, an extremely aggressive cancer, causes the most skin cancer-related deaths, due to metastasis to other areas of the body, such as lymph nodes, lungs, liver, brain or bone. It is characterized by high levels of matrix metalloproteinase (MMP)-2 and -9 secretions that degrade the extracellular matrix and basement membrane, allowing cancer cells to spread to distal organs. Various cytokines, mitogens, growth factors, inducers and inhibitors control MMP activities. We investigated the roles of these in regulation of MMP-2 and -9 in human melanoma A-2058 cells...
April 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440462/imperatorin-efficiently-blocks-tnf-%C3%AE-mediated-activation-of-ros-pi3k-akt-nf-%C3%AE%C2%BAb-pathway
#12
Ke Si Wang, Ying Lv, Zhe Wang, Juan Ma, Chunliu Mi, Xuezheng Li, Guang Hua Xu, Lian Xun Piao, Sheng Zhe Zheng, Xuejun Jin
Inflammation contributes to development and progression in a variety of cancers, including cervical cancer, which is the second leading cause of cancer deaths in women worldwide. In this study, we examined the anti-inflammatory effects of imperatorin, a psoralen-type furanocoumarin from the fruits of Angelica dahurica, in tumor necrosis factor-α (TNF-α)-stimulated HeLa cells by investigating its impact on the production and expression of cytokines and the major signal-transduction pathways. We found this compound significantly inhibited the TNF-α-induced expression of NF-κB target genes, such as COX-2, cyclin  D1, MMP-9, VEGF, IL-6 and Bcl-xL in a concentration-dependent manner...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28438834/rankl-cytokine-enhances-tnf-induced-osteoclastogenesis-independently-of-tnf-receptor-associated-factor-traf-6-by-degrading-traf3-in-osteoclast-precursors
#13
Zhenqiang Yao, Wei Lei, Rong Duan, Yanyun Li, Lu Luo, Brendan F Boyce
Cytokines, including receptor activator of nuclear factor kappa B ligand (RANKL) and TNF, induce increased osteoclast (OC) formation and bone loss in postmenopausal osteoporosis and inflammatory arthritides. RANKL and TNF can independently induce OC formation in vitro from WT OC precursors via TNF receptor-associated factor (TRAF) adaptor proteins, which bind to their receptors. Of these, only TRAF6 is required for RANKL-induced osteoclastogenesis in vitro. However, the molecular mechanisms involved remain incompletely understood...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28438557/the-isozyme-selective-phosphodiesterase-4-inhibitor-abi-4-attenuates-the-effects-of-lipopolysaccharide-in-human-cells-and-rodent-models-of-peripheral-and-cns-inflammation
#14
Joseph R Hedde, Ashley N Hanks, Christopher J Schmidt, Zoë A Hughes
Inhibitors of phosphodiesterase-4 (PDE4) have been approved for the treatment of inflammatory disorders, but are associated with dose-limiting nausea and vomiting. These side effects are hypothesized to be mediated by inhibition of the PDE4D isozyme. Here we demonstrate the anti-inflammatory effects of the novel brain penetrant PDE4D-sparing PDE4 inhibitor, ABI-4. ABI-4 was a potent (EC50 ∼14 nM) inhibitor of lipopolysaccharide (LPS) induced TNF-α release from mouse microglia and human PBMCs. ABI-4 (0.32 mg/kg) blocked LPS-induced release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in blood and brain of mice...
April 21, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28438162/targeting-of-nicotinamide-phosphoribosyltransferase-enzymatic-activity-ameliorates-lung-damage-induced-by-ischemia-reperfusion-in-rats
#15
Geng-Chin Wu, Wen-I Liao, Shu-Yu Wu, Hsin-Ping Pao, Shih-En Tang, Min-Hui Li, Kun-Lun Huang, Shi-Jye Chu
BACKGROUND: Emerging evidence reveals that nicotinamide phosphoribosyltransferase (NAMPT) has a significant role in the pathophysiology of the inflammatory process. NAMPT inhibition has a beneficial effect in the treatment of a variety of inflammatory diseases. However, it remains unclear whether NAMPT inhibition has an impact on ischemia-reperfusion (I/R)-induced acute lung injury. In this study, we examined whether NAMPT inhibition provided protection against I/R lung injury in rats...
April 24, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28437280/inhibition-of-rho-kinase-attenuates-left-ventricular-remodeling-caused-by-chronic-intermittent-hypoxia-in-rats-via-suppressing-myocardial-inflammation-and-apoptosis
#16
Zhi-Hua Wang, Die Zhu, Sheng Xie, Yan Deng, Yueying Pan, Jie Ren, Hui-Guo Liu
Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea syndrome (OSAS), has been reported to play a key role in the development of OSAS-associated cardiovascular diseases including cardiac remodeling. RhoA/Rho-kinase (ROCK) pathway has also been implicated in myocardial remodeling, but the exact mechanisms are not fully elucidated. The current study's purpose is to investigate the influence of fasudil, a selective ROCK inhibitor, on CIH-induced left ventricular remodeling in rats and its possible mechanisms...
April 18, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28433945/cqmuh-011-a-novel-adamantane-sulfonamide-compound-inhibits-lipopolysaccharide-and-d-galactosamine-induced-fulminant-hepatic-failure-in-mice
#17
Liping Yan, Xiangnan Hu, Qihong Wu, Rong Jiang, Sisi Zhang, Qiao Ling, Hailin Liu, Xuejun Jiang, Jingyuan Wan, Yingju Liu
CQMUH-011, a novel adamantane sulfonamide compound, was shown to suppress macrophage activation and proliferation in our previous study. However, it is unknown whether CQMUH-011 has anti-inflammatory and hepatoprotective properties. In this study, we investigated the potential effects and mechanisms of CQMUH-011 on lipopolysaccharide (LPS)-induced RAW264.7 cell activation in vitro and LPS- and D-galactosamine (D-GalN)-induced fulminant hepatic failure (FHF) in vivo. The results showed that in RAW264.7 cells challenged by LPS, CQMUH-011 inhibited cell proliferation and induced cell cycle arrest and apoptosis...
April 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28433746/transforming-growth-factor-beta-1-signaling-regulates-neuroinflammation-and-apoptosis-in-mild-traumatic-brain-injury
#18
Rachel K Patel, Nithisha Prasad, Ram Kuwar, Debanjan Haldar, P M Abdul-Muneer
Mild Traumatic brain injury (mTBI) is a low-level injury, which often remains undiagnosed, and in most cases it leads to death and disability as it advances as secondary injury. Therefore, it is important to study the underlying signaling mechanisms of mTBI-associated neurological ailments. While transforming growth factor-beta1 (TGF-β1) has a significant role in inflammation and apoptosis in myriads of other pathophysiological conditions, the precise function of increased TGF-β1 after mTBI is unknown. In this study, our objective is to study the physiological relevance and associated mechanisms of TGF-β1-mediated inflammation and apoptosis in mTBI...
April 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28433552/roscovitine-attenuates-intimal-hyperplasia-via-inhibiting-nf-%C3%AE%C2%BAb-and-stat3-activation-induced-by-tnf-%C3%AE-in-vascular-smooth-muscle-cells
#19
Ming He, Chao Wang, Jia-Huan Sun, Yu Liu, Hong Wang, Jing-Shan Zhao, Yun-Feng Li, Hong Chang, Jian-Ming Hou, Jun-Na Song, Ai-Ying Li, En-Sheng Ji
Roscovitine is a selective CDK inhibitor originally designed as anti-cancer agent, which has also been shown to inhibit proliferation in vascular smooth muscle cells (VSMCs). However, its effect on vascular remodeling and its mechanism of action remain unknown. In our study, we created a new intimal hyperplasia model in male Sprague-Dawley rats by trypsin digestion method, which cause to vascular injury as well as the model of rat carotid balloon angioplasty. Roscovitine administration led to a significant reduction in neointimal formation and VSMCs proliferation after injury in rats...
April 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28433514/cox-2-inhibition-potentiates-mouse-bone-marrow-stem-cell-engraftment-and-differentiation-mediated-wound-repair
#20
Ramasatyaveni Geesala, Neha R Dhoke, Amitava Das
BACKGROUND: Engraftment of transplanted stem cells is often limited by cytokine and noncytokine proinflammatory mediators at the injury site. We examined the role of Cyclooxygenase-2 (Cox-2)-induced cytokine-mediated inflammation on engraftment of transplanted bone marrow stem cells (BMSCs) at the wound site. METHODS: BMSCs isolated from male C57/BL6J mice were transplanted onto excisional splinting wounds in syngenic females in presence or absence of celecoxib, Cox-2 specific inhibitor (50 mg/kg, body weight [b wt]), to evaluate engraftment and wound closure...
April 19, 2017: Cytotherapy
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