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Il-1 receptor antagonist

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https://www.readbyqxmd.com/read/29141858/interleukin-1-blockade-in-recently-decompensated-systolic-heart-failure-results-from-redhart-recently-decompensated-heart-failure-anakinra-response-trial
#1
Benjamin W Van Tassell, Justin Canada, Salvatore Carbone, Cory Trankle, Leo Buckley, Claudia Oddi Erdle, Nayef A Abouzaki, Dave Dixon, Dinesh Kadariya, Sanah Christopher, Aaron Schatz, Jessica Regan, Michele Viscusi, Marco Del Buono, Ryan Melchior, Pranav Mankad, Juan Lu, Robin Sculthorpe, Giuseppe Biondi-Zoccai, Edward Lesnefsky, Ross Arena, Antonio Abbate
BACKGROUND: An enhanced inflammatory response predicts worse outcomes in heart failure (HF). We hypothesized that administration of IL-1 (interleukin-1) receptor antagonist (anakinra) could inhibit the inflammatory response and improve peak aerobic exercise capacity in patients with recently decompensated systolic HF. METHODS AND RESULTS: We randomly assigned 60 patients with reduced left ventricular ejection fraction (<50%) and elevated C-reactive protein levels (>2 mg/L), within 14 days of hospital discharge, to daily subcutaneous injections with anakinra 100 mg for 2 weeks, 12 weeks, or placebo...
November 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29141788/interleukin-1-receptor-antagonist-and-2-5-oligoadenylate-synthetase-like-molecules-as-novel-biomarkers-for-multiple-sclerosis-patients-in-bahrain
#2
Moudi Al-Nashmi, Safa Taha, Isa Alsharoqi, Moiz Bakhiet
BACKGROUND: Multiple sclerosis (MS) is a multi-factorial disease of the Central Nervous System (CNS) affecting young adults leading to significant disabilities over time. MS is now believed to be prevalent in Arabian Gulf area with high incidence due to environmental factors and unknown genetic variations. The objectives of this study was to detect up-regulated potential genes that might be involved in neuroinflammatory process in MS patients in Bahrain and to measure the protein levels of the expressed genes...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141125/elevated-proinflammatory-markers-in-22q11-2-deletion-syndrome-are-associated-with-psychosis-and-cognitive-deficits
#3
Ehud Mekori-Domachevsky, Michal Taler, Yehuda Shoenfeld, Michael Gurevich, Polina Sonis, Omri Weisman, Abraham Weizman, Doron Gothelf
OBJECTIVE: 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder whose phenotype includes high rates of a schizophrenia-like psychotic disorder and immune system abnormalities. Thus, 22q11.2DS is an ideal model for studying the relationship between psychosis and inflammation. The aim of the present study was to identify inflammatory markers that may play a role in the pathophysiologic pathways associated with psychosis and cognitive deficits in 22q11.2DS. METHODS: Forty-nine individuals with 22q11...
November 14, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/29138810/angiotensin-converting-enzyme-2-angiotensin-1-7-mas-axis-prevents-pancreatic-acinar-cell-inflammatory-response-via-inhibition-of-the-p38-mitogen-activated-protein-kinase-nuclear-factor-%C3%AE%C2%BAb-pathway
#4
Xiaozheng Yu, Lijian Cui, Fei Hou, Xiaoya Liu, Yan Wang, Yan Wen, Cheng Chi, Chunyun Li, Ruixia Liu, Chenghong Yin
The aim of the present study was to investigate the role of the angiotensin-converting enzyme (ACE)2-angiotensin‑(Ang)-(1-7)-Mas axis in the pathogenesis of pancreatitis and the association between this axis and the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor (NF-κB) signaling pathway in pancreatic acinar cells. Mouse pancreatic acinar cancer (MPC-83) cells were stimulated with 10 nM caerulein (CAE) to create an in vitro model of acute pancreatitis, and collected for analysis at 2, 6, 12, 24 and 48 h post stimulation...
November 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29133043/1-4-naphthoquinones-potently-inhibiting-p2x7-receptor-activity
#5
R X Faria, F H Oliveira, J P Salles, A S Oliveira, N L von Ranke, M L Bello, C R Rodrigues, H C Castro, A R Louvis, D L Martins, V F Ferreira
P2X7 receptor (P2X7R) is an ATP-gated ion-channel with potential therapeutic applications. In this study, we prepared and searched a series of 1,4-naphthoquinones derivatives to evaluate their antagonistic effect on both human and murine P2X7 receptors. We explored the structure-activity relationship and binding mode of the most active compounds using a molecular modeling approach. Biological analysis of this series (eight analogues and two compounds) revealed significant in vitro inhibition against both human and murine P2X7R...
October 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29131694/role-of-neuron-glial-interaction-mediated-by-il-1%C3%AE-in-ectopic-tooth-pain
#6
H Komiya, K Shimizu, N Noma, Y Tsuboi, K Honda, K Kanno, K Ohara, M Shinoda, B Ogiso, K Iwata
Although many reports have demonstrated that ectopic pain develops in the orofacial region following tooth pulp inflammation, which often causes misdiagnosis and inappropriate treatment for patients with pulpitis, the precise mechanism remains unknown. In the present study, we hypothesized that the functional interaction between satellite glial cells and neurons mediated by interleukin 1β (IL-1β) in the trigeminal ganglion (TG) is involved in ectopic orofacial pain associated with tooth pulp inflammation...
November 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29129760/the-key-role-of-proinflammatory-cytokines-matrix-proteins-rankl-opg-and-wnt-%C3%AE-catenin-in-bone-healing-of-hip-arthroplasty-patients
#7
Jean Cassuto, Agnetha Folestad, Jan Göthlin, Henrik Malchau, Johan Kärrholm
INTRODUCTION: We still lack understanding of why some implants fail while most remain stable after decades of use. Proinflammatory cytokines, matrix proteins and bone regulating cytokines of the RANKL/OPG (receptor activator of nuclear factor kappa B ligand/osteoprotegerin) and Wnt/β-catenin pathways are mandatory for normal bone repair but their spatial and temporal role in the healing of primary total hip arthroplasties (THA) has not been previously shown. MATERIALS AND METHODS: Twenty-four osteoarthritis patients with one-sided well-fixed primary THA were prospectively monitored during 18years (18Y) with repeated blood samples, clinical variables and radiographs...
November 9, 2017: Bone
https://www.readbyqxmd.com/read/29119534/angiotensin-ii-causes-neuronal-damage-in-stretch-injured-neurons-protective-effects-of-losartan-an-angiotensin-t1-receptor-blocker
#8
P M Abdul-Muneer, Saurav Bhowmick, Nicholas Briski
Angiotensin II (Ang II) is a mediator of oxidative stress via activation/induction of reactive oxygen and nitrogen species-generating enzymes, NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS). We investigated the hypothesis that overproduction of Ang II during traumatic brain injury (TBI) induces the activation of the oxidative stress, which triggers neuroinflammation and cell apoptosis in a cell culture model of neuronal stretch injury. We first established that stretch injury causes a rapid increase in the level of Ang II, which causes the release of pro-inflammatory cytokines, IL-1β and TNF-α, via the induction of oxidative stress...
November 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29115421/gene-expression-profiles-and-protein%C3%A2-protein-interaction-networks-during-tongue-carcinogenesis-in-the-tumor-microenvironment
#9
Wei Sun, Zeting Qiu, Wenqi Huang, Minghui Cao
Oral tongue squamous cell carcinoma (OTSCC) has a high incidence and is associated with a high mortality rate. Studies regarding the potential molecular mechanism of OTSCC in the tumor microenvironment (TME) are required. The present study aimed to perform bioinformatic analysis to identify important nodes, clusters and functional pathways during tongue carcinogenesis in the TME. After downloading the gene expression data of GSE42780, differentially expressed genes (DEGs) among carcinoma, dysplastic and normal samples in epithelia and fibroblasts were identified using the affy and limma packages with R version 3...
October 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29113143/sevoflurane-postconditioning-induced-anti-inflammation-via-inhibition-of-the-toll-like-receptor-4-nuclear-factor-kappa-b-pathway-contributes-to-neuroprotection-against-transient-global-cerebral-ischemia-in-rats
#10
Jung-Won Hwang, Young-Tae Jeon, Young-Jin Lim, Hee-Pyoung Park
The anti-inflammatory actions of sevoflurane postconditioning are suggested as an important mechanism of sevoflurane postconditioning-induced neuroprotection against cerebral ischemia. Here, we determined whether the anti-inflammatory effects of sevoflurane postconditioning were mediated via inhibition of the toll-like receptor (TLR)-4/nuclear factor kappa B (NF-κB) pathway after global transient cerebral ischemia in rats. Forty-five rats were randomly assigned to five groups as follows: (1) control (10 min of ischemia, n = 10); (2) sevoflurane postconditioning (two periods of sevoflurane inhalation after ischemia for 10 min with a wash period of 10 min, n = 10); (3) resatorvid (intraperitoneal injection of a selective TLR-4 antagonist (3 mg/kg) 30 min before ischemia, n = 10); (4) sevoflurane postconditioning plus resatorvid (n = 10), and sham (n = 5)...
November 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29108858/increased-expression-of-type-1-cannabinoid-cb1-receptor-among-patients-with-rotator-cuff-lesions-and-shoulder-stiffness
#11
Shu-Jui Kuo, Feng-Sheng Wang, Jih-Yang Ko, Chih-Hsin Tang, Ka-Kit Siu, Ya-Hung Hsu, Tsai-Chen Tsai
BACKGROUND: Shoulder stiffness is a disease manifested by pain, limited range of motion, and functional disability. The inflammatory and fibrosis processes play a substantial role in the pathogenesis of shoulder stiffness. The CB1 receptor has been recognized to mediate the processes of pathologic fibrosis. This study investigated the role of the CB1 pathway in pathogenesis of rotator cuff lesions with shoulder stiffness. METHODS: All of the patients undergoing repair surgery for rotator cuff lesions were recruited and subcategorized into subjects with and without shoulder stiffness...
November 3, 2017: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/29105312/acute-effect-of-a-resistance-exercise-session-on-markers-of-cartilage-breakdown-and-inflammation-in-women-with-rheumatoid-arthritis
#12
Ana Carolina Pereira Nunes Pinto, Jamil Natour, Charlles Heldan de Moura Castro, Marina Eloi, Império Lombardi Junior
AIM: To assess the acute effect of resistance exercise (RE) on circulating biomarkers of cartilage breakdown and inflammation in women with rheumatoid arthritis (RA). METHODS: Thirty-four volunteers (17 with and 17 without RA), participated in a 25 min RE session (knee extension, knee flexion, hip abduction and hip adduction) with one set of 12 repetitions at 50% of one repetition maximum (1RM) and one set of eight repetitions at 75% of 1RM. Blood samples were collected 30 and 5 min before, immediately after and 1, 2 and 24 h after the session...
November 3, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/29103192/lipid-peroxidation-and-immune-biomarkers-are-associated-with-major-depression-and-its-phenotypes-including-treatment-resistant-depression-and-melancholia
#13
Magdalena Sowa-Kućma, Krzysztof Styczeń, Marcin Siwek, Paulina Misztak, Rafał J Nowak, Dominika Dudek, Janusz K Rybakowski, Gabriel Nowak, Michael Maes
To examine immune-inflammatory and oxidative (I&O) biomarkers in major depression (MDD) and its related phenotypes, we recruited 114 well-phenotyped depressed patients and 50 healthy controls and measured serum levels of interleukin (IL)-1α, soluble IL-1 receptor antagonist (sIL-1RA), soluble IL-2 receptor (sIL-2R), soluble IL-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 60 and 80 kDa (sTNF-R1/R2), and thiobarbituric acid reactive substances (TBARS). Obtained results indicate that MDD is characterized by increased sIL-1RA, sTNF-R1, and TBARS concentrations...
November 4, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29098911/targeted-treatments-for-hidradenitis-suppurativa-a-review-of-the-current-literature-and-ongoing-clinical-trials
#14
Melody Maarouf, Ashley K Clark, Dylan E Lee, Vivian Y Shi
PURPOSE: Targeted, immune-modulating drugs are at the forefront of therapy for HS, and a comprehensive clinical trial registry is needed to facilitate data pooling and clinical efficacy comparison. MATERIALS AND METHODS: A systematic review of the ClinicalTrials.gov database was searched for planned, in-progress, completed, or terminated trials investigating the effect of targeted biologic therapies for hidradenitis suppurativa (HS). When results of RCTs were not available, case reports or series were included...
November 10, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29097738/pharmacologically-induced-reversible-hypometabolic-state-mitigates-radiation-induced-lethality-in-mice
#15
Subhajit Ghosh, Namita Indracanti, Jayadev Joshi, Jharna Ray, Prem Kumar Indraganti
Therapeutic hypothermia has proven benefits in critical care of a number of diseased states, where inflammation and oxidative stress are the key players. Here, we report that adenosine monophosphate (AMP) triggered hypometabolic state (HMS), 1-3 hours after lethal total body irradiation (TBI) for a duration of 6 hours, rescue mice from radiation-induced lethality and this effect is mediated by the persistent hypothermia. Studies with caffeine and (6)N-cyclohexyladenosine, a non-selective antagonist and a selective agonist of adenosine A1 receptor (A1AR) respectively, indicated the involvement of adenosine receptor (AR) signaling...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29094325/the-expression-of-matrix-metalloproteinases-and-their-inhibitors-in-corneal-fibroblasts-by-alarmins-from-necrotic-corneal-epithelial-cells
#16
Akira Iwatake, Akira Murakami, Nobuyuki Ebihara
PURPOSE: Sterile ulceration is frequently observed in the cornea following persistent corneal epithelial damage. We examined the effect of alarmins released by necrotic corneal epithelial cells (HCE) on the production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) by corneal fibroblasts. METHODS: IL-1α and high-mobility group box 1 protein (HMGB1) released into the supernatant derived from necrotic HCE cells were measured with enzyme-linked immunosorbent assay (ELISA)...
November 1, 2017: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29094311/tocilizumab-a-review-in-rheumatoid-arthritis
#17
Lesley J Scott
Intravenous (IV) and subcutaneous (SC) tocilizumab (RoActemra(®)), an IL-6 receptor antagonist, are approved (± methotrexate) in numerous countries throughout the world, for the treatment of adults with moderate to severe active rheumatoid arthritis (RA). Extensive clinical experience has firmly established the short- and long-term efficacy and safety of tocilizumab [monotherapy or in combination with conventional synthetic DMARDs (csDMARDs)] in adults with early-stage and longer-duration established RA...
November 2017: Drugs
https://www.readbyqxmd.com/read/29094161/inflammatory-biomarkers-and-risk-of-schizophrenia-a-2-sample-mendelian-randomization-study
#18
Fernando Pires Hartwig, Maria Carolina Borges, Bernardo Lessa Horta, Jack Bowden, George Davey Smith
Importance: Positive associations between inflammatory biomarkers and risk of psychiatric disorders, including schizophrenia, have been reported in observational studies. However, conventional observational studies are prone to bias, such as reverse causation and residual confounding, thus limiting our understanding of the effect (if any) of inflammatory biomarkers on schizophrenia risk. Objective: To evaluate whether inflammatory biomarkers have an effect on the risk of developing schizophrenia...
November 1, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/29091309/epiregulin-ereg-is-upregulated-through-an-il-1%C3%AE-autocrine-loop-in-caco-2-epithelial-cells-with-reduced-cftr-function
#19
Macarena Massip-Copiz, Mariángeles Clauzure, Ángel G Valdivieso, Tomás A Santa-Coloma
CFTR is a cAMP-regulated chloride channel, whose mutations produce cystic fibrosis. The impairment of CFTR activity increases the intracellular Cl(-) concentration, which in turn produces an increased interleukin-1β (IL-1β) secretion. The secreted IL-1β then induces an autocrine positive feedback loop, further stimulating IL-1β priming and secretion. Since IL-1β can transactivate the epidermal growth factor receptor (EGFR), we study here the levels of expression for different EGFR ligands in Caco-2/pRS26 cells (expressing shRNA against CFTR resulting in a reduced CFTR expression and activity)...
November 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29080833/age-related-immune-responses-after-burn-and-inhalation-injury-are-associated-with-altered-clinical-outcomes
#20
John H Frankel, Devin M Boe, Joslyn M Albright, Eileen B O'Halloran, Stewart R Carter, Christopher S Davis, Luis Ramirez, Ellen L Burnham, Richard L Gamelli, Majid Afshar, Elizabeth J Kovacs
This prospective study aimed to address changes in inflammatory response between different aged populations of patients who sustained burn and inhalation injury. Plasma and bronchoalveolar lavage (BAL) samples were collected from 104 patients within 15h of their estimated time of burn injury. Clinical variables, laboratory parameters, and immune mediator profiles were examined in association with clinical outcomes. Older patients were at higher odds for death after burn injury (odds ratio (OR)=7.37 per 10years, p=0...
October 26, 2017: Experimental Gerontology
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