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https://www.readbyqxmd.com/read/28087575/treating-inflammation-and-infection-in-the-21st-century-new-hints-from-decoding-resolution-mediators-and-mechanisms
#1
REVIEW
Charles N Serhan
Practitioners of ancient societies from the time of Hippocrates and earlier recognized and treated the signs of inflammation, heat, redness, swelling, and pain with agents that block or inhibit proinflammatory chemical mediators. More selective drugs are available today, but this therapeutic concept has not changed. Because the acute inflammatory response is host protective to contain foreign invaders, much of today's pharmacopeia can cause serious unwanted side effects, such as immune suppression. Uncontrolled inflammation is now considered pathophysiologic and is associated with many widely occurring diseases such as cardiovascular disease, neurodegenerative diseases, diabetes, obesity, and asthma, as well as classic inflammatory diseases (e...
January 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28087294/bioactive-metabolites-of-docosahexaenoic-acid
#2
REVIEW
Ondrej Kuda
Docosahexaenoic acid (DHA) is an essential fatty acid that is recognized as a beneficial dietary constituent and as a source of the anti-inflammatory specialized proresolving mediators (SPM): resolvins, protectins and maresins. Apart from SPMs, other metabolites of DHA also exert potent biological effects. This article summarizes current knowledge on the metabolic pathways involved in generation of DHA metabolites. Over 70 biologically active metabolites have been described, but are often discussed separately within specific research areas...
January 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28081163/income-in-multiple-sclerosis-patients-with-different-disease-phenotypes
#3
Andrius Kavaliunas, Ali Manouchehrinia, Virginija Danylaite Karrenbauer, Hanna Gyllensten, Anna Glaser, Kristina Alexanderson, Jan Hillert
BACKGROUND: Multiple sclerosis (MS) is a disease with profound heterogeneity in clinical course. OBJECTIVE: To analyze sources and levels of income among MS patients in relation to disease phenotype with a special focus on identifying differences/similarities between primary progressive MS (PPMS) and secondary progressive MS (SPMS). METHODS: A total of 6890 MS patients aged 21-64 years and living in Sweden in 2010 were identified for this cross-sectional study...
2017: PloS One
https://www.readbyqxmd.com/read/28079976/maresin-1-induces-a-novel-pro-resolving-phenotype-in-human-platelets
#4
Katie L Lannan, Sherry L Spinelli, Neil Blumberg, Richard P Phipps
BACKGROUND: Antiplatelet therapy is a cornerstone of modern medical practice and is routinely employed to reduce the likelihood of myocardial infarction, thrombosis, and stroke. However, current antiplatelet therapies, such as aspirin, often have adverse side effects, including increased risk of bleeding, and some patients are relatively "aspirin-resistant". Platelets are intimately involved in hemostasis and inflammation, and clinical consequences are associated with excessive or insufficient platelet activation...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28078314/onset-of-secondary-progressive-ms-after-long-term-rituximab-therapy-a-case-report
#5
H-Christian von Büdingen, Antje Bischof, Erica L Eggers, Shengzhi Wang, Carolyn J Bevan, Bruce A C Cree, Roland G Henry, Stephen L Hauser
A patient with relapsing multiple sclerosis (RMS) was treated with a standard immunomodulatory therapy, but due to ongoing disease activity was switched to rituximab. Relapses ceased, but secondary progressive MS (SPMS) eventually appeared, associated with new focal spinal cord white matter lesions. Cerebrospinal fluid (CSF) showed persistent oligoclonal bands (OCB) and clonally related B cells in CSF and peripheral blood. The treatment escalation approach failed to prevent evolution to SPMS, raising the question of whether initiation of B-cell depleting therapy at the time of RMS diagnosis should be tested to more effectively address the immune pathology leading to SPMS...
January 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28045953/double-blind-controlled-randomized-trial-of-cyclophosphamide-versus-methylprednisolone-in-secondary-progressive-multiple-sclerosis
#6
Bruno Brochet, Mathilde S A Deloire, Paul Perez, Timothé Loock, Louise Baschet, Marc Debouverie, Sophie Pittion, Jean-Christophe Ouallet, Pierre Clavelou, Jérôme de Sèze, Nicolas Collongues, Patrick Vermersch, Hélène Zéphir, Giovanni Castelnovo, Pierre Labauge, Christine Lebrun, Mikael Cohen, Aurélie Ruet
BACKGROUND: Therapeutic options are limited in secondary progressive multiple sclerosis (SPMS). Open-label studies suggested efficacy of monthly IV cyclophosphamide (CPM) without induction for delaying progression but no randomized trial was conducted so far. OBJECTIVE: To compare CPM to methylprednisolone (MP) in SPMS. METHODS: Randomized, double-blind clinical trial on two parallel groups. Patient with SPMS, with a documented worsening of the Expanded Disability Status Scale (EDSS) score during the last year and an EDSS score between 4·0 and 6·5 were recruited and received one intravenous infusion of treatment (CPM: 750 mg /m2 body surface area-MP: 1g) every four weeks for one year, and every eight weeks for the second year...
2017: PloS One
https://www.readbyqxmd.com/read/28035846/employment-and-absenteeism-in-working-age-persons-with-multiple-sclerosis
#7
Amber Salter, Nina Thomas, Tuula Tyry, Gary Cutter, Ruth Ann Marrie
AIMS: To better understand the impact of the clinical course of multiple sclerosis (MS) and disability on employment, absenteeism, and related factors. MATERIALS AND METHODS: We included respondents to the North American Research Committee on Multiple Sclerosis Registry spring 2015 update survey who were United States or Canadian residents, aged 18-65 years and reported having relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS)...
December 30, 2016: Journal of Medical Economics
https://www.readbyqxmd.com/read/28017890/rigidity-of-polymer-micelles-affects-interactions-with-tumor-cells
#8
Tal Stern, Inon Kaner, Neta Laser Zer, Hila Shoval, Dvir Dror, Zakhariya Manevitch, Liraz Chai, Yifat Brill-Karniely, Ofra Benny
Controlling the interaction of drug delivery systems (DDS) with tissues is critical for the success of therapies. Specifically in cancer, due to the high density of the tumors, tissue penetration of DDS is critical and may be challenging. In previous work we have shown that Solidified Polymer Micelles (SPMs) rapidly internalize into cells and tissues. Using AFM analysis, in the present work we measured differences in rigidity of SPM compared with Wet Polymer Micelles (WPM). We further examined whether the semi-solid form of hydrated SPMs has an effect on the interaction with tumor cells both in mono-layer systems and in multi-layer clusters of cells as spheroids...
December 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28017240/focal-muscle-vibration-an-effective-rehabilitative-approach-in-severe-gait-impairment-due-to-multiple-sclerosis
#9
F Camerota, C Celletti, E Di Sipio, C De Fino, C Simbolotti, M Germanotta, M Mirabella, L Padua, V Nociti
Gait impairment is one of the most frequent and life-altering consequences of Multiple sclerosis (MS), frequently associated with lower limb spasticity. Focal muscle vibration (fMV) is a technique that applies a vibratory stimulus to a specific muscle or its tendon, reducing spasticity. The aim of our study is to evaluate the efficacy of fMV in ameliorating gait impairment in MS patients with severe lower limb spasticity, measured by Gait Analysis (GA) and objective and patient-oriented scales scores. Fourteen patients affected by Secondary Progressive MS (SPMS) with a lower limb spasticity with a low or no response to antispastic drugs, received repetitive fMV (r-fMV) over the quadriceps and the lumbar paraspinal muscles...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28002074/resolving-inflammation-by-using-nutrition-therapy-roles-for-specialized-proresolving-mediators
#10
Lucy V Norling, Lucy Ly, Jesmond Dalli
PURPOSE OF REVIEW: Inflammation is a unifying component of many of the diseases that afflict Western civilizations. Nutrition therapy and, in particular, essential fatty acid supplementation is one of the approaches that is currently in use for the treatment and management of many inflammatory conditions. The purpose of the present review is to discuss the recent literature in light of the discovery that essential fatty acids are converted by the body to a novel genus of lipid mediators, termed specialized proresolving mediators (SPMs)...
December 20, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/27996064/free-serum-haemoglobin-is-associated-with-brain-atrophy-in-secondary-progressive-multiple-sclerosis
#11
Alex Lewin, Shea Hamilton, Aviva Witkover, Paul Langford, Richard Nicholas, Jeremy Chataway, Charles R M Bangham
Background A major cause of disability in secondary progressive multiple sclerosis (SPMS) is progressive brain atrophy, whose pathogenesis is not fully understood. The objective of this study was to identify protein biomarkers of brain atrophy in SPMS. Methods We used surface-enhanced laser desorption-ionization time-of-flight mass spectrometry to carry out an unbiased search for serum proteins whose concentration correlated with the rate of brain atrophy, measured by serial MRI scans over a 2-year period in a well-characterized cohort of 140 patients with SPMS...
November 15, 2016: Wellcome Open Res
https://www.readbyqxmd.com/read/27984234/fine-tuning-inflammation-resolution-programs-focus-on-atherosclerosis
#12
Gabrielle Fredman, Sudeshna Sadhu, Nicholas Rymut
PURPOSE OF REVIEW: Nonresolving inflammation is now considered the underpinning of several prevalent human diseases, including atherosclerosis. The resolution of inflammation is a highly coordinated program to counterbalance proinflammatory signals for a swift return to tissue homeostasis. This process is controlled in part by endogenous specialized proresolving lipid mediators (SPMs). Emerging evidence has revealed that the balance of SPMs and proinflammatory mediators during acute inflammation regulates the duration of the inflammatory response and the timing of tissue resolution...
December 15, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/27964946/predicting-the-effect-of-amino-acid-single-point-mutations-on-protein-stability-large-scale-validation-of-md-based-relative-free-energy-calculations
#13
Thomas Steinbrecher, Chongkai Zhu, Lingle Wang, Robert Abel, Christopher Negron, David Pearlman, Eric Feyfant, Jianxin Duan, Woody Sherman
The stability of folded proteins is critical to their biological function and for the efficacy of protein therapeutics. Predicting the energetic effects of protein mutations can improve our fundamental understanding of structural biology, the molecular basis of diseases, and possible routes to addressing those diseases with biological drugs. Identifying the effect of single amino acid point mutations on the thermodynamic equilibrium between the folded and unfolded states of a protein can pinpoint residues of critical importance that should be avoided in the process of improving other properties (affinity, solubility, viscosity, etc...
December 10, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27956559/clinical-course-of-multiple-sclerosis-a-nationwide-cohort-study
#14
Ali Manouchehrinia, Omid Beiki, Jan Hillert
BACKGROUND: The course of multiple sclerosis (MS) has been studied in several cohorts; however, results have varied significantly. OBJECTIVE: To describe the clinical course of MS in a nationwide cohort of patients. METHOD: Data from the Swedish MS register (SMSreg) were used to estimate the median time to the sustained Expanded Disability Status Scale (EDSS) scores 3.0, 4.0 and 6.0, onset of secondary progressive multiple sclerosis (SPMS) and death using Kaplan-Meier method...
December 12, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/27943187/isolation-of-synaptosomes-synaptic-plasma-membranes-and-synaptic-junctional-complexes
#15
Mary L Michaelis, Lei Jiang, Elias K Michaelis
Isolation of synaptic nerve terminals or synaptosomes provides an opportunity to study the process of neurotransmission at many levels and with a variety of approaches. For example, structural features of the synaptic terminals and the organelles within them, such as synaptic vesicles and mitochondria, have been elucidated with electron microscopy. The postsynaptic membranes are joined to the presynaptic "active zone" of transmitter release through cell adhesion molecules and remain attached throughout the isolation of synaptosomes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27935580/second-malignancies-in-the-context-of-lenalidomide-treatment-an-analysis-of-2732-myeloma-patients-enrolled-to-the-myeloma-xi-trial
#16
J R Jones, D A Cairns, W M Gregory, C Collett, C Pawlyn, R Sigsworth, A Striha, R Henderson, M F Kaiser, M Jenner, G Cook, N H Russell, C Williams, G Pratt, B Kishore, J Lindsay, M T Drayson, F E Davies, K D Boyd, R G Owen, G H Jackson, G J Morgan
We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4-1.0%), 2.3% (95% CI 1.6-2.7%) and 3.8% (95% CI 2.9-4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (P=0...
December 9, 2016: Blood Cancer Journal
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
#17
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 MX 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 MX. During single cycle of the MX therapy a dose of 12 mg/m(2) of body surface area was administered and next cycles every three months up to a total dose of 140 mg/m(2) were realized...
December 23, 2016: International Journal of Neuroscience
https://www.readbyqxmd.com/read/27882837/determining-multiple-sclerosis-phenotype-from-electronic-medical-records
#18
Richard E Nelson, Jorie Butler, Joanne LaFleur, Kristin Knippenberg, Aaron W C Kamauu, Scott L DuVall
BACKGROUND: Multiple sclerosis (MS), a central nervous system disease in which nerve signals are disrupted by scarring and demyelination, is classified into phenotypes depending on the patterns of cognitive or physical impairment progression: relapsing-remitting MS (RRMS), primary-progressive MS (PPMS), secondary-progressive MS (SPMS), or progressive-relapsing MS (PRMS). The phenotype is important in managing the disease and determining appropriate treatment. The ICD-9-CM code 340.0 is uninformative about MS phenotype, which increases the difficulty of studying the effects of phenotype on disease...
December 2016: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/27864218/second-primary-malignancies-in-multiple-myeloma-an-overview-and-imwg-consensus
#19
REVIEW
P Musto, K C Anderson, M Attal, P G Richardson, A Badros, J Hou, R Comenzo, J Du, B G M Durie, J San Miguel, H Einsele, W M Chen, L Garderet, G Pietrantuono, J Hillengass, R A Kyle, P Moreau, J J Lahuerta, O Landgren, H Ludwig, A Larocca, A Mahindra, M Cavo, A Mazumder, P L McCarthy, A Nouel, S V Rajkumar, A Reiman, E R Serra, O Sezer, E Terpos, I Turesson, S Usmani, B M Weiss, A Palumbo
BACKGROUND: Therapeutic advancements following the introduction of autologous stem cell transplantation and 'novel' agents have significantly improved clinical outcomes for patients with multiple myeloma (MM). Increased life expectancy, however, has led to renewed concerns about the long-term risk of second primary malignancies (SPMs). This review outlines the most up-to-date knowledge of possible host-, disease-, and treatment-related risk factors for the development of SPMs in patients with MM, and provides practical recommendations to assist physicians...
November 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27860411/secondary-primary-malignancies-during-the-lenalidomide-dexamethasone-regimen-in-relapsed-refractory-multiple-myeloma-patients
#20
Rouslan Kotchetkov, Esther Masih-Khan, Chia-Min Chu, Eshetu G Atenafu, Christine Chen, Vishal Kukreti, Suzanne Trudel, Rodger Tiedemann, Donna E Reece
Lenalidomide in combination with dexamethasone (Len-dex) represents a highly effective treatment in relapsed/refractory multiple myeloma (RRMM) patients. However, an increased risk of secondary primary malignancies (SPMs), including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) has been described in patients receiving lenalidomide. In order to assess the incidence and features of this complication, we reviewed 195 patients with RRMM treated with Len-dex at our institution. The median follow-up time from diagnosis of MM was 73 months (10-234 months) and from initiation of Len-dex was 19 months (1-104 months)...
November 18, 2016: Cancer Medicine
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