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Lieselot Decroix, Cajsa Tonoli, Elodie Lespagnol, Constantino Balestra, Amandine Descat, Marie Jose Drittij-Reijnders, Jamie R Blackwell, Wilhelm Stahl, Andrew M Jones, Antje R Weseler, Aalt Bast, Romain Meeusen, Elsa Heyman
INTRODUCTION: During exercise in hypoxia, O2 delivery to brain and muscle is compromised and oxidative stress is elicited. Cocoa flavanols (CF) have antioxidant capacities and can increase blood flow by stimulating endothelial function. We aimed to examine the effects of 7-day CF intake on oxidative stress, nitric oxide production and tissue oxygenation in response to exercise in hypoxia (14.3% O2 ). METHODS: In a randomized, double blind, cross-over study, 14 well-trained male cyclists completed 4 trials: exercise in normoxia or hypoxia, after 7-day CF or placebo intake...
March 15, 2018: Journal of Applied Physiology
A L Fedele, L Petricca, B Tolusso, S Alivernini, S Canestri, C Di Mario, S L Bosello, G Ferraccioli, E Gremese
OBJECTIVES: To define baseline clinical and immunological characteristics [anti-citrullinated peptide antibodies (ACPAs), immunoglobulin M (IgM)- and IgA-rheumatoid factor (RF), and interleukin-6 (IL-6) levels] involved in determining baseline erosiveness, outcome, and radiographic progression among seropositive and seronegative early rheumatoid arthritis (ERA) patients. METHOD: The 408 ERA patients enrolled in the study were monitored every 3 months according to the treat-to-target strategy...
March 15, 2018: Scandinavian Journal of Rheumatology
Lazaros I Sakkas, Dimitrios P Bogdanos
PURPOSE OF REVIEW: This review highlights the most recent data obtained in this field and provides clues toward the better understanding of the close interplay between microbiota and host, leading to autoimmune diseases. RECENT FINDINGS: A well-described model of microbiota/host interaction of relevance to autoimmunity is that linking anti-citrullinated peptide antibody positive rheumatoid arthritis and alterations of microbiota largely concentrating on Porphyromonas gingivalis and more recently of Aggregatibacter actinomycetemcomitans and Prevotella copri...
March 13, 2018: Current Opinion in Rheumatology
Ismet H Bajraktari, Blerim Krasniqi, Sylejman Rexhepi, Sadi Bexheti, Elton Bahtiri, Halit Bajraktari, Besim Luri
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterised by intra-articular and extra-articular manifestations but very rarely with coxitis. AIM: This study aimed to investigate the prevalence of coxitis, clinical changes, and its correlation with the parameters of inflammatory activity. METHODS: A cohort of 951 patients diagnosed with ACR/EULAR (American College of Rheumatology/European League against Rheumatism) 2010 criteria was enrolled in this prospective, observational and analytic research study...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
Li Yunchun, Wang Yue, Fang Zhong Jun, Su Qizhu, Ding Liumei
OBJECTIVES: To investigate the serum level of Myeloid-Related Protein 8/14 complex (MRP8/14) and to predict and monitor the response to biologic treatment in rheumatoid arthritis (RA) patients. METHODS: Each patient underwent clinical examination and blood sampling for assessment of serum high-sensitivity C-reactive protein (hs-CRP) levels, erythrocyte sedimentation rate (ESR), rheumatoid factors (RF), anti-cyclic citrullinated protein antibodies (anti-CCP), and serum concentrations of MRP8/14 protein complexes (myeloid-related proteins, MRP8/14) were measured at baseline, and weeks 4 and 12 (after initiation of treatment)...
January 2018: Annals of Clinical and Laboratory Science
Silvia D Visonà, Onno J de Boer, Claire Mackaaij, Hans H de Boer, Kartika R Pertiwi, Ruben W de Winter, Antonio Osculati, Allard C van der Wal
Acute medial dissection of aorta can occur in the context of a sudden and unexpected death. For medico-legal reasons it is important to estimate as accurately the histological age of dissections. We evaluated the additional value of a systematic application of immunohistochemistry, compared with conventional histology only, in determining chronological steps of injury and repair. Thirty two paraffin embedded specimens of aortic dissection were retrospectively allocated to one of four defined stages: acute (I), subacute (II), early organizing (III) and scarring (IV) using Hematoxylin and Eosin and Elastica van Gieson stained sections...
February 10, 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Johanna Sigaux, Jérôme Biton, Emma André, Luca Semerano, Marie-Christophe Boissier
Pollution has long been incriminated in many cardiovascular and respiratory diseases. More recently, studies evaluated the potential role for particulate pollutants in autoimmune diseases, including rheumatoid arthritis (RA). The incidence of RA was found to be higher in urban areas. Living near air pollution emitters was associated with higher risks of developing RA and of producing RA-specific autoantibodies. Nevertheless, no strong epidemiological evidence exists to link one or more specific air pollution particles to RA...
March 7, 2018: Joint, Bone, Spine: Revue du Rhumatisme
Meghdad Abdollahpour-Alitappeh, Seyed Masoud Hashemi Karouei, Majid Lotfinia, Amir Amanzadeh, Mahdi Habibi-Anbouhi
Rituximab is a chimeric monoclonal antibody directed against B-lymphocyte specific antigen CD20, which is used for the treatment of B-cell malignancies. However, the effectiveness of rituximab is limited partly due to treatment resistance. The aim of this study was to develop rituximab-based antibody drug conjugate (ADC) to enhance rituximab activity. In this study, monomethyl auristatin E (MMAE) was covalently conjugated to dithiothreitol -reduced rituximab via a valine-citrulline peptide linker (rituximab-vcMMAE)...
March 9, 2018: Artificial Cells, Nanomedicine, and Biotechnology
K H Lee, L Cavanaugh, H Leung, F Yan, Z Ahmadi, B H Chong, F Passam
INTRODUCTION: Neutrophil extracellular traps (NETs) are networks of extracellular fibres produced from neutrophil DNA with a pathogenic role in infection, thrombosis and other conditions. Reliable assays for measuring NETs are desirable as novel treatments targeting NETs are being explored for the treatment of these conditions. We compare a whole blood flow cytometry method with serum assays to measure NETs-associated markers in patients with sepsis and thrombosis. METHODS: Patients with deep venous thrombosis (n = 25), sepsis (n = 21) and healthy controls (n = 23) were included in the study...
March 9, 2018: International Journal of Laboratory Hematology
Santanu Mondal, Sangram S Parelkar, Mitesh Nagar, Paul R Thompson
Protein Arginine deiminases (PADs) play an important role in the pathogenesis of various diseases, including rheumatoid arthritis, multiple sclerosis, lupus, ulcerative colitis and breast cancer. Therefore, the development of PAD-inhibitors has drawn significant research interest in recent years. Herein, we describe the development of the first photoswitchable PAD-inhibitors. These compounds possess an azobenzene photoswitch to optically control PAD activity. Screening of a series of inhibitors structurally similar to BB-Cl-Amidine afforded compounds 1 and 2 as the most promising candidates for the light-controlled inhibition of PAD2; the cis-isomer of 1 is 10-fold more potent than its trans-isomer, whereas the trans-isomer of 2 is 45-fold more potent than the corresponding cis-isomer...
March 8, 2018: ACS Chemical Biology
Sarah Twigg, Elena Nikiphorou, Jackie L Nam, Laura Hunt, Kulveer Mankia, Peta Elizabeth Pentony, Jane E Freeston, Ai Lyn Tan, Paul Emery
Objectives: To compare comorbidities in a cohort of cyclic citrullinated peptide (CCP) antibody positive patients without or prior to onset of inflammatory arthritis (IA) to those in patients with early IA. Methods: Baseline data from two established cohorts were used. The first recruited people at risk of IA: CCP antibody positive cases without IA (CCP Cohort, n  = 296). The second cohort [the Inflammatory Arthritis CONtinuum study (IACON)] recruited patients with early IA ( n  = 725)...
2018: Frontiers in Medicine
Isabel Lopez-Oliva, Akshay D Paropkari, Shweta Saraswat, Stefan Serban, Zehra Yonel, Praveen Sharma, Paola de Pablo, Karim Raza, Andrew Filer, Iain Chapple, Thomas Dietrich, Melissa M Grant, Purnima S Kumar
OBJECTIVES: Studies that demonstrate an association between rheumatoid arthritis (RA) and dysbiotic oral microbiomes are often confounded by the presence of extensive periodontitis in these individuals. Therefore, the present investigation sought to investigate the role of RA in modulating the periodontal microbiome by comparing periodontally healthy individuals with and without RA. METHODS: Subgingival plaque was collected from was collected periodontally healthy individuals (22 with and 19 without RA), and 16S gene sequenced on the Ilumina MiSeq platform...
March 7, 2018: Arthritis & Rheumatology
Katy A Lloyd, Johanna Steen, Khaled Amara, Philip J Titcombe, Lena Israelsson, Susanna L Lundström, Diana Zhou, Roman A Zubarev, Evan Reed, Luca Piccoli, Cem Gabay, Antonio Lanzavecchia, Dominique Baeten, Karin Lundberg, Daniel L Mueller, Lars Klareskog, Vivianne Malmström, Caroline Grönwall
Autoreactive B cells have a central role in the pathogenesis of rheumatoid arthritis (RA), and recent findings have proposed that anti-citrullinated protein autoantibodies (ACPA) may be directly pathogenic. Herein, we demonstrate the frequency of variable-region glycosylation in single-cell cloned mAbs. A total of 14 ACPA mAbs were evaluated for predicted N-linked glycosylation motifs in silico, and compared to 452 highly-mutated mAbs from RA patients and controls. Variable region N-linked motifs (N-X-S/T) were strikingly prevalent within ACPA (100%) compared to somatically hypermutated (SHM) RA bone marrow plasma cells (21%), and synovial plasma cells from seropositive (39%) and seronegative RA (7%)...
March 7, 2018: European Journal of Immunology
Hadi Bazzazi, Mehrdad Aghaei, Ali Memarian, Hossein Asgarian-Omran, Nasser Behnampour, Yaghoub Yazdani
The Th17, Th1 and dual Th17/Th1 cells are important players in rheumatoid arthritis (RA) disease. To assess their roles, the frequency and impact of these cells were investigated in patients with different disease activity. In 14 new cases and 41 established RA patients in comparison with 22 healthy controls, the percentages of Th17, Th1 and dual Th17/Th1 cells were determined by flow-cytometry and their correlations were investigated with disease activity score (DAS28). Moreover, serum levels of IL-6 and IL-17 as inducer and functional cytokines for Th17 were investigated...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
Konstantinos C Fragkos, Alastair Forbes
Background: Citrulline has been described as a marker of intestinal function or absorption but evidence varies according to clinical settings. Objective: The objective of this article is to examine the evidence of plasma citrulline as a marker of intestinal function and absorption in various clinical settings. Methods: Studies were examined for p values, means and standard deviations, correlation coefficients or other metrics depicting the association of citrulline with intestinal function...
March 2018: United European Gastroenterology Journal
Yongzhi Wang, Lingtao Luo, Oscar Ö Braun, Johannes Westman, Raed Madhi, Heiko Herwald, Matthias Mörgelin, Henrik Thorlacius
Abdominal sepsis is associated with dysfunctional hemostasis. Thrombin generation (TG) is a rate-limiting step in systemic coagulation. Neutrophils can expell neutrophil extracellular traps (NETs) and/or microparticles (MPs) although their role in pathological coagulation remains elusive. Cecal ligation and puncture (CLP)-induced TG in vivo was reflected by a reduced capacity of plasma from septic animals to generate thrombin. Depletion of neutrophils increased TG in plasma from CLP mice. Sepsis was associated with increased histone 3 citrullination in neutrophils and plasma levels of cell-free DNA and DNA-histone complexes and administration of DNAse not only eliminated NET formation but also elevated TG in sepsis...
March 5, 2018: Scientific Reports
Giorgio Gabarrini, Laura M Palma Medina, Tim Stobernack, Rianne C Prins, Marines du Teil Espina, Jeroen Kuipers, Monika A Chlebowicz, John W A Rossen, Arie Jan van Winkelhoff, Jan Maarten van Dijl
The oral pathogen Porphyromonas gingivalis is one of the major periodontal agents and it has been recently hailed as a potential cause of the autoimmune disease rheumatoid arthritis. In particular, the peptidylarginine deiminase enzyme of P. gingivalis (PPAD) has been implicated in the citrullination of certain host proteins and the subsequent appearance of antibodies against citrullinated proteins, which might play a role in the etiology of rheumatoid arthritis. The aim of this study was to investigate the extracellular localization of PPAD in a large panel of clinical P...
January 1, 2018: Virulence
Jin-Ju Byeon, Min-Ho Park, Seok-Ho Shin, Byeong Ill Lee, Yuri Park, Jangmi Choi, Nahye Kim, Yeonjae Kang, Young G Shin
A single hybrid affinity-captured-LC-TOF-MS/MS method was developed and applied for the quantification of total antibody, antibody conjugated drug and free payload of antibody drug conjugate (ADC). Adcetris®, one of the valine-citrulline MMAE (vc-MMAE) conjugated ADC, was used as a model ADC compound. A quadratic regression (weighted 1/concentration) was used to fit calibration curves over the concentration range of 30.65-613.00 ng/mL with an equation y=ax2 +bx+c for the acDrug of Adcetris®. The qualification run met the acceptance criteria of ± 25% accuracy and precision values for quality control samples...
March 5, 2018: Biomedical Chromatography: BMC
Brenna S Fullerton, Cristine S Velazco, Charles R Hong, Alexandra N Carey, Tom Jaksic
PURPOSE: Severe combined immunodeficiency (SCID) screening by T-cell receptor excision circles (TREC) has been part of Massachusetts routine newborn screening since 2009. Tetratricopeptide repeat domain 7A gene (TTC7A) mutations responsible for hereditary multiple intestinal atresia with combined immunodeficiency (MIA-CID) were also recently identified. We reviewed newborn SCID screening among infants with intestinal failure and correlated results with patient characteristics and outcomes...
January 2018: JPEN. Journal of Parenteral and Enteral Nutrition
Olivier Bouillanne, Jean-Claude Melchior, Cécile Faure, Muriel Paul, Florence Canouï-Poitrine, Yves Boirie, Didier Chevenne, Christine Forasassi, Ester Guery, Stéphane Herbaud, Philippe Le Corvoisier, Nathalie Neveux, Valérie Nivet-Antoine, Alain Astier, Agathe Raynaud-Simon, Stéphane Walrand, Luc Cynober, Christian Aussel
BACKGROUND: Citrulline (CIT), is not extracted by the splanchnic area, can stimulate muscle protein synthesis and could potentially find clinical applications in conditions involving low amino acid (AA) intake, such as in malnourished older subjects. OBJECTIVE: Our purpose was to research the effects of CIT supplementation on protein metabolism in particular on non-oxidative leucine disposal (NOLD, primary endpoint), and splanchnic extraction of amino acids in malnourished older patients...
February 21, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
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