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Disease modifying drugs

Z Mbese, B A Aderibigbe
BACKGROUND: Carvacrol is the major constituent of essential oils derived from plants. It exhibits antimicrobial, antioxidant, anticancer, anti-inflammatory, and anticholinesterase activity. The analogues of carvacrol can be prepared via selected synthetic routes, resulting in potent compounds. OBJECTIVE: Modifying carvacrol by the introduction of selected functionalities has the potential to enhance the biological activity of carvacrol. The functionalities on carvacrol such as the hydroxyl group, benzene ring and alkyl groups can be modified or used for hybridization with important pharmaceutical scaffolds...
December 4, 2018: Recent Patents on Anti-infective Drug Discovery
S P Mohanty, M Pai Kanhangad, B Yogesh Kumar, A Singh
PURPOSE: The present study evaluated the clinical and radiological outcomes in patients with tuberculosis of the thoracic and thoracolumbar spine, treated by an operative technique in which anterior debridement with posterior instrumentation and global fusion was performed through a single-stage posterior approach. METHODS: Ninty-seven patients with spinal tuberculosis, between T1 and L1, in whom anterior debridement, bone grafting, with posterior instrumentation and fusion was performed through a single-stage posterior approach, with a minimum follow-up of 2 years, formed the basis of this study...
December 4, 2018: Musculoskeletal Surgery
Victor M Rivera
Multiple sclerosis (MS) has become a common neurological disorder involving populations previously considered to be infrequently affected. Genetic dissemination from high- to low-risk groups is a determining influence interacting with environmental and epigenetic factors, mostly unidentified. Disease modifying therapies (DMT) are effective in treating relapsing MS in variable degrees; one agent is approved for primary progressive disease, and several are in development. In the era of high-efficacy medications, complex molecules, and monoclonal antibodies (MAB), including anti-VLA4 (natalizumab), anti-CD52 (alemtuzumab), and anti-CD20 (ocrelizumab), obtaining NEDA (no evidence of disease activity) becomes an elusive accomplishment in areas of the world where access to MS therapies and care are generally limited...
November 30, 2018: Biomedicines
M Pisa, P Della Valle, A Coluccia, V Martinelli, G Comi, A D'Angelo, L Moiola
Alemtuzumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS). During the immune reconstitution following the use of this treatment severe secondary autoimmune diseases (SADs) can develop. We present the case of a patient affected by active MS who failed to achieve disease control with several disease-modifying drugs and was thereafter successfully treated with alemtuzumab, obtaining no evidence of disease activity and a high quality of life. Twenty months after the first infusion of alemtuzumab the patient developed acquired haemophilia A (AHA), a treatable but potentially lifethreatening condition that should be considered a possible SADs associated to this drug...
November 29, 2018: Multiple Sclerosis and related Disorders
Cissy Kityo, Alexander J Szubert, Abraham Siika, Robert Heyderman, Mutsa Bwakura-Dangarembizi, Abbas Lugemwa, Shalton Mwaringa, Anna Griffiths, Immaculate Nkanya, Sheila Kabahenda, Simon Wachira, Godfrey Musoro, Chatu Rajapakse, Timothy Etyang, James Abach, Moira J Spyer, Priscilla Wavamunno, Linda Nyondo-Mipando, Ennie Chidziva, Kusum Nathoo, Nigel Klein, James Hakim, Diana M Gibb, A Sarah Walker, Sarah L Pett
BACKGROUND: In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events...
December 2018: PLoS Medicine
Kristy M Shaeer, Monika T Zmarlicka, Elias B Chahine, Nicholas Piccicacco, Jonathan C Cho
Plazomicin is a novel aminoglycoside antibiotic that binds to the bacterial 30S ribosomal subunit, thus inhibiting protein synthesis via a concentration-dependent manner. Plazomicin displays a broad spectrum of activity against aerobic gram-negative bacteria, including extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and organisms with aminoglycoside-modifying enzymes. In a large phase III clinical trial, plazomicin was shown to be noninferior to meropenem in the treatment of complicated urinary tract infections (cUTI) with respect to the coprimary efficacy endpoints of the microbiologically modified intent-to-treat composite cure rate at day 5 (plazomicin 88% [n=168/191] vs meropenem 91...
December 4, 2018: Pharmacotherapy
Ankita Singh, Pradeepta Sekhar Patro, Amita Aggarwal
INTRODUCTION: Rheumatoid arthritis (RA) patients have high expression levels of hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p in peripheral blood. We studied if baseline blood levels of these microRNAs (miRNAs) could predict response to methotrexate (MTX). METHODS: RA patients (the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria) with active disease (disease-modifying anti-rheumatic drug (DMARD)-naïve and Disease Activity Score 28 (DAS28) > 3...
December 3, 2018: Clinical Rheumatology
Kirstine S Tølbøl, Birgit Stierstorfer, Jörg F Rippmann, Sanne S Veidal, Kristoffer T G Rigbolt, Tanja Schönberger, Matthew P Gillum, Henrik H Hansen, Niels Vrang, Jacob Jelsing, Michael Feigh, Andre Broermann
BACKGROUND: There is a marked need for improved animal models of nonalcoholic steatohepatitis (NASH) to facilitate the development of more efficacious drug therapies for the disease. METHODS: Here, we investigated the development of fibrotic NASH in male Wistar rats fed a choline-deficient L-amino acid-defined (CDAA) diet with or without cholesterol supplementation for subsequent assessment of drug treatment efficacy in NASH biopsy-confirmed rats. The metabolic profile and liver histopathology were evaluated after 4, 8, and 12 weeks of dieting...
December 3, 2018: Digestive Diseases and Sciences
Gabriel Bsteh, Laura Algrang, Harald Hegen, Michael Auer, Sebastian Wurth, Franziska Di Pauli, Florian Deisenhammer, Thomas Berger
BACKGROUND: Multiple sclerosis (MS) predominantly affects women of child-bearing potential. Pregnancy in MS is still a controversial issue lacking standardized treatment recommendations. OBJECTIVE: To examine the reciprocal effects of pregnancy, MS, and disease-modifying treatment (DMT). METHODS: We analyzed 387 pregnancies in 239 women with relapsing remitting multiple sclerosis (RRMS) and ⩾1 pregnancy, establishment of diagnosis >1 year before conception, and ⩾2 years of follow-up after delivery...
December 3, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Erika Darrah, Fang Yu, Laura C Cappelli, Antony Rosen, James R O'Dell, Ted R Mikuls
OBJECTIVE: To determine if the baseline presence of autoantibodies to peptidylarginine deiminase 4 (PAD4) predicts therapeutic response to biologic and conventional disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who failed methotrexate (MTX) monotherapy. METHODS: Baseline serum from 282 RA patients who failed MTX monotherapy were screened for the presence of anti-PAD4 antibodies by immunoprecipitation. Clinical response to either triple DMARD (MTX, sulfasalazine, and hydroxychloroquine) or MTX-etanercept combination therapy was determined at 24- and 48-weeks post-treatment initiation...
December 3, 2018: Arthritis & Rheumatology
Marcel Gebhardt, Peter Kropp, Frank Hoffmann, Uwe K Zettl
Multiple sclerosis (MS) is the most common immune-mediated inflammatory disease of the central nervous system (CNS). Early diagnosis and treatment is important to prevent progression of disability in the course of the chronic disease. Therefore, correct and fast identification of early symptoms is vital. Headache is generally not recognized as an early symptom of MS, although numerous studies could show a high prevalence of headache in MS patients. The most common misdiagnosis is migraine. The aim of this study is to investigate the prevalence as well as the phenomenology of headache in MS especially with regard to the progression of the disease...
November 30, 2018: Journal of Neural Transmission
Yu Zhou, Yukio Yamamura, Masatoshi Ogawa, Ryosuke Tsuji, Koichiro Tsuchiya, Jiro Kasahara, Satoshi Goto
Parkinson's disease (PD) is caused by a progressive degeneration of nigral dopaminergic cells leading to striatal dopamine deficiency. From the perspective of antiparkinsonian drug mechanisms, pharmacologic treatment of PD can be divided into symptomatic and disease-modifying (neuroprotective) therapies. An increase in the level and activity of the Abelson non-receptor tyrosine kinase (c-Abl) has been identified in both human and mouse brains under PD conditions. In the last decade, it has been observed that the inhibition of c-Abl activity holds promise for protection against the degeneration of nigral dopaminergic cells in PD and thereby exerts antiparkinsonian effects...
2018: Frontiers in Pharmacology
Jennifer L Griffith, Michael Wong
Nearly a third of patients with epilepsy have seizures refractory to current medical therapies. In the search for novel drug targets, the mTOR pathway has emerged as key in the regulation of neuronal function, growth and survival, and other cellular processes related to epileptogenesis. Hyperactivation of the mTOR pathway has been implicated in tuberous sclerosis complex and other 'mTORopathies', clinical syndromes associated with cortical developmental malformations and drug-resistant epilepsy. Recently published clinical trials of mTOR inhibitors in tuberous sclerosis complex have shown that these drugs are effective at decreasing seizure frequency...
May 2018: Future Neurology
Melanie Hagen, Matthias Englbrecht, Judith Haschka, Michaela Reiser, Arnd Kleyer, Axel Hueber, Bernhard Manger, Camille Figueiredo, Jayme Fogagnolo Cobra, Hans-Peter Tony, Stephanie Finzel, Stefan Kleinert, Jörg Wendler, Florian Schuch, Monika Ronneberger, Martin Feuchtenberger, Martin Fleck, Karin Manger, Wolfgang Ochs, Hans-Martin Lorenz, Hubert Nüsslein, Rieke Alten, Jörg Henes, Klaus Krüger, Georg Schett, Jürgen Rech
OBJECTIVE: To analyze the effect of a risk-stratified disease-modifying antirheumatic drug (DMARD)-tapering algorithm based on multibiomarker disease activity (MBDA) score and anticitrullinated protein antibodies (ACPA) on direct treatment costs for patients with rheumatoid arthritis (RA) in sustained remission. METHODS: The study was a posthoc retrospective analysis of direct treatment costs for 146 patients with RA in sustained remission tapering and stopping DMARD treatment, in the prospective randomized RETRO study...
December 1, 2018: Journal of Rheumatology
Dong Hyuk Lee, Peter Lee, Sang Won Seo, Jee Hoon Roh, Minyoung Oh, Jungsu S Oh, Seung Jun Oh, Jae Seung Kim, Yong Jeong
The concept of cognitive reserve (CR) originated from discrepancies between the degree of brain pathology and the severity of clinical manifestations. CR has been characterized through CR proxies, such as education and occupation complexity; however, such approaches have inherent limitations. Although several methods have been developed to overcome these limitations, they fail to reflect the entire Alzheimer's disease (AD) pathology. Meanwhile, graph theory analysis, one of most powerful and flexible approaches, have established remarkable network properties of the brain...
November 29, 2018: NeuroImage
Violeta Balbas-Martinez, Robin Michelet, Andrea N Edginton, Kevin Meesters, Iñaki F Trocóniz, An Vermeulen
In a recent multicenter population pharmacokinetic study of ciprofloxacin administered to children suffering from complicated urinary tract infection (cUTI), the apparent volume of distribution (Vd ) and total plasma clearance (CL) were decreased by 83.6% and 41.5% respectively, compared to healthy children. To understand these differences, a physiologically-based pharmacokinetic model (PBPK) for ciprofloxacin was developed for cUTI children. First, a PBPK model in adults was developed, modified incorporating age-dependent functions and evaluated with paediatric data generated from a published model in healthy children...
November 29, 2018: European Journal of Pharmaceutical Sciences
Farzana Hakim, Amir Rashid, Amer Fakhr, Saleem Ahmed Khan
OBJECTIVE: To evaluate matrix metalloproteinase-9 gene expression in rheumatoid arthritis patients on disease modifying anti-rheumatic agents with the objective to further modify the current treatment regimen if indicated in order to prevent progression to deforming rheumatoid arthritis. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: CREAM Lab (Centre for Research in Experimental and Applied Medicine) and Department of Biochemistry and Molecular Biology, Army Medical College, in collaboration with Rheumatology Department at Military Hospital Rawalpindi from November 2015 to November 2016...
December 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Rachel Archer, Emma Hock, Jean Hamilton, John Stevens, Munira Essat, Edith Poku, Mark Clowes, Abdullah Pandor, Matt Stevenson
BACKGROUND: Rheumatoid arthritis (RA) is a chronic, debilitating disease associated with reduced quality of life and substantial costs. It is unclear which tests and assessment tools allow the best assessment of prognosis in people with early RA and whether or not variables predict the response of patients to different drug treatments. OBJECTIVE: To systematically review evidence on the use of selected tests and assessment tools in patients with early RA (1) in the evaluation of a prognosis (review 1) and (2) as predictive markers of treatment response (review 2)...
November 2018: Health Technology Assessment: HTA
Anna Haduch, Władysława Anna Daniel
The current state of knowledge indicates that the cerebral cytochrome P450 (CYP) plays an important role in the endogenous metabolism in the brain. Different CYP isoenzymes mediate metabolism of many endogenous substrates, such as monoaminergic neurotransmitters, neurosteroids, cholesterol, vitamins and arachidonic acid. Therefore, these enzymes may affect brain development, susceptibility to mental and neurodegenerative diseases and may contribute to their pathophysiology. In addition, they can modify the therapeutic effects of psychoactive drugs at the place of their target action in the brain, where the drugs can act by affecting the metabolism of endogenous substrates...
December 2, 2018: Drug Metabolism Reviews
Anne-Laure Flamar, Henri Bonnabau, Sandra Zurawski, Christine Lacabaratz, Monica Montes, Laura Richert, Aurelie Wiedemann, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Lauren Hudacik, Andres Salazar, Cécile Peltekian, Rodolphe Thiebaut, Gerard Zurawski, Yves Levy
HIV-1 infection can be controlled by anti-retroviral drug therapy, but this is a lifetime treatment and the virus remains latent and rapidly rebounds if therapy is stopped. HIV-1-infected individuals under this drug regimen have increased rates of cancers, cardiovascular diseases, and autoimmunity due to compromised immunity. A therapeutic vaccine boosting cellular immunity against HIV-1 is therefore desirable and, possibly combined with other immune modulating agents, could obviate the need for long-term drug therapies...
2018: PloS One
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