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https://www.readbyqxmd.com/read/27924938/the-secretome-of-periodontal-ligament-stem-cells-from-ms-patients-protects-against-eae
#1
Thangavelu Soundara Rajan, Sabrina Giacoppo, Francesca Diomede, Patrizia Ballerini, Michele Paolantonio, Marco Marchisio, Adriano Piattelli, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
Manipulation of stem cells or stem cells-derived secretome has emerged as a novel alternative therapeutic option for multiple sclerosis (MS). Here we show that human periodontal ligament stem cells (hPDLSCs)-derived conditioned medium (hPDLSCs-CM) and purified exosomes/microvesicles (hPDLSCs-EMVs) obtained from Relapsing Remitting (RR)-MS patients and healthy donors block experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing anti-inflammatory and immunosuppressive effects in spinal cord and spleen, and reverse disease progression by restoring tissue integrity via remyelination in the spinal cord...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924587/qualitative-and-quantitative-proteome-analysis-of-oral-fluids-in-health-and-periodontal-disease-by-mass-spectrometry
#2
Erdjan Salih
The significance of protein identification and characterization by classical protein chemistry approaches is clearly highlighted by our detailed understanding of the biological systems assembled over a time period of almost a century. The advent of state-of-the-art mass spectrometry (MS) with sensitivity, speed, and global protein analysis capacity without individual protein purification has transformed the classical protein chemistry with premise to accelerate discovery. These combined with the ability of the oral fluids such as whole saliva (WS) and gingival crevicular fluid (GCF) to reflect both systemic and locally derived proteins have generated significant interest to characterize these fluids more extensively by MS technology...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27923714/brief-report-acquired-braf-v600e-mutation-as-resistant-mechanism-after-treatment-with-osimertinib
#3
Chao-Chi Ho, Wei-Yu Liao, Chih-An Lin, Jin-Yuan Shih, Chong-Jen Yu, James Chih-Hsin Yang
INTRODUCTION: AZD9291 (osimertinib) is designed for acquired T790M mutation after first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been used. Some of the resistance mechanisms that present after osimertinib treatment, including a newly acquired EGFR C797S mutation, have been identified. It is unclear, however, whether the bypass pathway is also a resistant mechanism in patients after osimertinib treatment. METHODS: Cells from malignant pleural effusion were collected and cultured at the time of progression in a patient being treated with osimertinib...
December 3, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27923633/diversity-of-glycosphingolipid-gm2-and-cholesterol-accumulation-in-npc1-patient-specific-ipsc-derived-neurons
#4
Michaela Trilck, Franziska Peter, Chaonan Zheng, Marcus Frank, Kostantin Dobrenis, Hermann Mascher, Arndt Rolfs, Moritz J Frech
Niemann-Pick disease Type C1 (NPC1) is a rare progressive neurodegenerative disorder caused by mutations in the NPC1 gene. On the cellular level NPC1 mutations lead to an accumulation of cholesterol and gangliosides. As a thorough analysis of the severely affected neuronal cells is unfeasible in NPC1 patients, we recently described the cellular phenotype of neuronal cells derived from NPC1 patient iPSCs carrying the compound heterozygous mutation c.1836A>C/c.1628delC. Here we expanded the analysis to cell lines carrying the prevalent mutation c...
December 3, 2016: Brain Research
https://www.readbyqxmd.com/read/27921460/direct-infusion-mass-spectrometry-for-metabolomic-phenotyping-of-diseases
#5
Raúl González-Domínguez, Ana Sayago, Ángeles Fernández-Recamales
Metabolomics based on direct mass spectrometry (MS) analysis, either by direct infusion or flow injection of crude sample extracts, shows a great potential for metabolic fingerprinting because of its high-throughput screening capability, wide metabolite coverage and reduced time of analysis. Considering that numerous metabolic pathways are significantly perturbed during the initiation and progression of diseases, these metabolomic tools can be used to get a deeper understanding about disease pathogenesis and discover potential biomarkers for early diagnosis...
January 2017: Bioanalysis
https://www.readbyqxmd.com/read/27921456/capillary-electrophoresis-mass-spectrometry-as-a-tool-for-untargeted-metabolomics
#6
Antonia García, Joanna Godzien, Ángeles López-Gonzálvez, Coral Barbas
Highly polar and ionic metabolites, such as sugars, most amino acids, organic acids or nucleotides are not retained by conventional reversed-phase LC columns and polar stationary phases and hydrophilic-interaction LC lacks of robustness, which is still limiting their applications for untargeted metabolomics where reproducibility is a must. Biological samples such as blood, urine or even tissues include many hydrophilic compounds secreted from cells, their analysis is essential for biomarker discovery, disease progression or treatment effects...
January 2017: Bioanalysis
https://www.readbyqxmd.com/read/27921221/safety-and-efficacy-of-natalizumab-in-japanese-patients-with-relapsing-remitting-multiple-sclerosis-open-label-extension-study-of-a-phase-2-trial
#7
Takahiko Saida, Jun-Ichi Kira, Shuji Kishida, Takashi Yamamura, Nobuhisa Ohtsuka, Yan Ling, Shinichi Torii, Nisha Lucas, Geoffrey Kuesters, Deb Steiner, J T Tibung
INTRODUCTION: The efficacy of natalizumab was evaluated in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) in a 24-week, phase 2 bridging study. An open-label, 2-year extension study from this trial was conducted to assess the safety and efficacy of natalizumab treatment in Japanese patients. METHODS: A total of 97 patients (43 previously on placebo; 54 previously on natalizumab) who had completed the bridging study were treated with 300 mg natalizumab every 4 weeks...
December 5, 2016: Neurology and Therapy
https://www.readbyqxmd.com/read/27920546/chronotherapy-with-low-dose-modified-release-prednisone-for-the-management-of-rheumatoid-arthritis-a-review
#8
REVIEW
Stefano Paolo Beltrametti, Aurora Ianniello, Clara Ricci
To date, rheumatoid arthritis (RA) remains a debilitating, life-threatening disease. One major concern is morning symptoms (MS), as they considerably impair the patients' quality of life and ability to work. MS change in a circadian fashion, resembling the fluctuations of inflammatory cytokines such as interleukin-6, whose levels are higher in RA patients compared to healthy donors. Conversely, serum levels of the potent anti-inflammatory glucocorticoid cortisol are similar to that of healthy subjects, suggesting an imbalance that sustains a pro-inflammatory state...
2016: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/27920164/epistemic-injustice-in-healthcare-encounters-evidence-from-chronic-fatigue-syndrome
#9
Charlotte Blease, Havi Carel, Keith Geraghty
Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) remains a controversial illness category. This paper surveys the state of knowledge and attitudes about this illness and proposes that epistemic concerns about the testimonial credibility of patients can be articulated using Miranda Fricker's concept of epistemic injustice. While there is consensus within mainstream medical guidelines that there is no known cause of CFS/ME, there is continued debate about how best to conceive of CFS/ME, including disagreement about how to interpret clinical studies of treatments...
December 5, 2016: Journal of Medical Ethics
https://www.readbyqxmd.com/read/27920149/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#10
Georgia Mandolesi, Francesca De Vito, Alessandra Musella, Antonietta Gentile, Silvia Bullitta, Diego Fresegna, Helena Sepman, Claudio Di Sanza, Nabila Haji, Francesco Mori, Fabio Buttari, Emerald Perlas, Maria Teresa Ciotti, Eran Hornstein, Irene Bozzoni, Carlo Presutti, Diego Centonze
: MicroRNAs (miRNA) play an important role in posttranscriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter pathology. However, little is known about their role in grey matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27919507/predictors-of-long-term-interferon-discontinuation-in-newly-diagnosed-relapsing-multiple-sclerosis
#11
Marcello Moccia, Raffaele Palladino, Antonio Carotenuto, Cinzia Valeria Russo, Maria Triassi, Roberta Lanzillo, Vincenzo Brescia Morra
BACKGROUND: Interferon-β has long-term safety and efficacy profiles for Relapsing Remitting Multiple Sclerosis (RRMS). However, the increasing number of available treatments requires to improve patient profiling and to perform individualized clinical decisions. Therefore, the present study investigated predictors of Interferon-β discontinuation. METHODS: The present retrospective observational cohort study included 499 newly diagnosed, drug naïve RRMS subjects receiving Interferon-β as first disease modifying treatment (DMT), during a 7...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27919495/clinical-characteristics-of-patients-with-multiple-sclerosis-enrolled-in-a-new-registry-in-egypt
#12
Magd Zakaria, Dina A Zamzam, Mohamed A Abdel Hafeez, Mahmoud S Swelam, Shaimaa S Khater, Mai F Fahmy, Ayman Abdel Hady, Mohamed M Fouad, Azza Abdel Nasser, Hany Aref, Mohsen Gadallah
BACKGROUND: Epidemiological studies of multiple sclerosis (MS) are lacking in Egypt. OBJECTIVE: To study the characteristics of Egyptian patients with multiple sclerosis in a new registry in a major tertiary referral centre in Cairo, Egypt. SUBJECT AND METHODS: Patients were from the project MS database of the Multiple Sclerosis Unit at Ain Shams University Hospitals (N=950). We conducted a detailed medical history and examination including the Expanded Disability Status Scale (EDSS)...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27919489/cognitive-event-related-potentials-in-multiple-sclerosis-correlation-with-mri-and-neuropsychological-findings
#13
Vasilios K Kimiskidis, Vasileios Papaliagkas, Kyriaki Sotirakoglou, Zoi K Kouvatsou, Victoria K Kapina, Efrosini Papadaki, Vaia Tsimourtou, Elvira Masoura, Dimitrios A Kazis, Sotirios Papayiannopoulos, Triantafyllos Geroukis, Sevasti Bostanjopoulou
BACKGROUND: Cognitive event-related potentials (ERPs) have been previously correlated with T2 lesion load (Τ2LL) in patients with multiple sclerosis (MS). It is currently unknown, however, whether ERPs also correlate with brain atrophy or the presence of T1 hypointense lesions ("black holes") which reflect tissue destruction and axonal loss. The primary aim of the current study is to explore the effect of neuroradiological parameters such as brain atrophy, T1 and T2 lesion load on auditory ERPs in MS patients...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27919477/practice-effect-in-symbol-digit-modalities-test-in-multiple-sclerosis-patients-treated-with-natalizumab
#14
Malte Roar, Zsolt Illes, Tobias Sejbaek
OBJECTIVES: How practice effect influences cognitive testing measured by monthly Symbol Digit Modalities Test (SDMT) during natalizumab treatment, and what factors confound such effect. METHODS: Eighty patients were examined monthly with SDMT for 26.2±8.4 months. After 26.0±8.1 months, SDMT was also performed with a rearranged key in 59 cases. Results of SDMTs with the rearranged and previous regular key were compared. We examined if gender, age, Extended Disability Status Scale (EDSS), relapses, and disability progression/improvement influence SDMT performed with the regular and the rearranged key, respectively...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27919195/efficacy-and-safety-of-mitoxantrone-use-in-primary-and-secondary-progressive-multiple-sclerosis-study-site-experience-based-on-the-therapy-of-104-patients
#15
Anetta Lasek-Bal, Karina Bartoszek, Arkadiusz Steposz, Przemyslaw Puz, Wieslaw Bal, Zofia Kazibutowska
Mitoxantrone (MX) is used in patients with primary and secondary progressive as well as relapsing-remitting type of multiple sclerosis (PPMS, SPMS, RRMS). The objective of our project was to evaluate the efficacy and safety of mitoxantrone use in patients with PPMS and SPMS. Methods The retrospective study included 104 patients (mean age 54.2 ± 9.0), with PPMS (13.46%) and SPMS (86.54%) treated with mitoxantrone. During single cycle of the MX therapy a dose of 12 mg/m2 of body surface area was administred and next cycles every three months up to a total dose of 140 mg/m2 were realized...
December 6, 2016: International Journal of Neuroscience
https://www.readbyqxmd.com/read/27918139/an-observational-study-to-assess-brain-mri-change-and-disease-progression-in-multiple-sclerosis-clinical-practice-the-ms-mrius-study
#16
Robert Zivadinov, Nasreen Khan, Jennie Medin, Pia Christoffersen, Jennifer Price, Jonathan R Korn, Ian Bonzani, Michael G Dwyer, Niels Bergsland, Ellen Carl, Diego Silva, Bianca Weinstock-Guttman
BACKGROUND & PURPOSE: To describe methodology, interim baseline, and longitudinal magnetic resonance imaging (MRI) acquisition parameter characteristics of the multiple sclerosis clinical outcome and MRI in the United States (MS-MRIUS). MATERIAL & METHODS: The MS-MRIUS is an ongoing longitudinal and retrospective study of MS patients on fingolimod. Clinical and brain MRI image scan data were collected from 600 patients across 33 MS centers in the United States. MRI brain outcomes included change in whole-brain volume, lateral ventricle volume, T2- and T1-lesion volumes, and new/enlarging T2 and gadolinium-enhancing lesions...
December 5, 2016: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/27917400/high-dose-biotin-treatment-for-secondary-progressive-multiple-sclerosis-may-interfere-with-thyroid-assays
#17
Alissa Minkovsky, Mark N Lee, Mitra Dowlatshahi, Trevor E Angell, Lilian S Mahrokhian, Athena K Petrides, Stacy E F Melanson, Ellen Marqusee, Whitney W Woodmansee
OBJECTIVE: To review cases and increase awareness in clinicians treating patients who may be taking biotin. METHODS: We describe the presentation and workup of a woman with secondary progressive multiple sclerosis on high dose biotin with laboratory studies suggestive of thyrotoxicosis. RESULTS: Plasma samples showed laboratory evidence of elevated thyroid hormone levels with elevated free thyroxine >7.8 ng/dl (reference interval (RI) 0...
2016: AACE Clin Case Rep
https://www.readbyqxmd.com/read/27915214/recent-advances-in-expanding-the-coverage-of-the-lipidome
#18
REVIEW
Sergey Tumanov, Jurre J Kamphorst
The lipidome comprises a large array of molecules with diverse physicochemical properties. Lipids are structural components of cells, act as a source of energy, and function as signaling mediators. Alterations in lipid metabolism are involved in the onset and progression of a variety of diseases, including metabolic syndrome and cancer. Because of this, interest in lipidomics, the comprehensive characterization of the lipidome by mass spectrometry, has intensified in recent years. However, obtaining a truly complete overview of all lipids in a sample has remained very challenging due to their enormous structural diversity...
December 1, 2016: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/27914464/immunogenicity-of-human-interferon-beta-containing-pharmaceuticals
#19
V D Nazarov, S V Lapin, A V Mazing, E P Evdoshenko, A A Totolian
Multiple sclerosis is a severe autoimmune disease with inflammatory component that continues to be resistant to treatment. One of the approaches retarding its progression is based on using nonspecific therapy with human interferon-beta (IFN-β)-containing pharmaceuticals. Neutralizing antibodies (NAbs) against genetically engineered pharmaceuticals developed by the patient's immune system, which reduce their therapeutic and biological activity, pose a serious problem. Cell lines sensitive to IFN-β activity also quantifying NAb level are applied because direct measurement of IFN-β antiviral activity is complicated...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27914034/identification-of-oxidized-phosphatidylinositols-present-in-oxldl-and-human-atherosclerotic-plaque
#20
Devin Hasanally, Andrea Edel, Rakesh Chaudhary, Amir Ravandi
Oxidized low-density lipoprotein (OxLDL) plays an important role in initiation and progression of atherosclerosis. Proatherogenic effects of OxLDL have been attributed to bioactive phospholipids generated during LDL oxidation. It is unknown what effect oxidation has on the phosphatidylinositol (PtdIns) molecules in LDL, even though PtdIns is 6% of the total LDL phospholipid pool. We sought to identify and quantitate oxidized phosphatidylinositol (OxPtdIns) species in OxLDL and human atherosclerotic plaque. Bovine liver PtdIns was subjected to non-enzymatic and lipoxygenase-catalyzed oxidation...
December 2, 2016: Lipids
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