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Drug tolerant persister

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https://www.readbyqxmd.com/read/29052906/evaluation-of-adherence-and-tolerability-of-prolonged-release-tacrolimus-advagraf-%C3%A2-in-kidney-transplant-patients-in-germany-a-multicenter-non-interventional-study
#1
Lukas J Lehner, Petra Reinke, Jan Hörstrup, Thomas Rath, Barbara Suwelack, Bernhard K Krämer, Klemens Budde, Bernhard Banas
This study assessed adherence to prolonged-release tacrolimus (PR-T)-based immunosuppression during routine maintenance of renal transplant recipients in Germany. Patients had received PR-T for ≥1 month at inclusion. Data were collected during four visits (V): baseline (V1), 6 (V2), 12 (V3) and 18 (V4) months. Composite primary endpoint: non-adherence at V4, defined as self-reported non-adherence on the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS©), investigator-rated non-adherence, and/or V4 tacrolimus trough level outside a pre-defined range...
October 20, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29022761/noninvasive-ocular-drug-delivery-system-of-dexamethasone-sodium-phosphate-in-the-treatment-of-experimental-uveitis-rabbit
#2
Kongnara Papangkorn, Eri Prendergast, John W Higuchi, Balbir Brar, William I Higuchi
PURPOSE: To investigate the efficacy and safety of dexamethasone sodium phosphate administered through Visulex system (DSP-Visulex) in treating experimental uveitis. METHODS: Uveitis was induced in rabbits by subcutaneous injections of complete Freund's adjuvant and an intravitreal injection of H37RA antigen. After induction, the animals of the control group received no treatment and the others received various treatment regimens of DSP-Visulex. Each regimen was different in DSP strength (4%, 8%, and 15%), application time, or treatment frequency...
October 12, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29022755/randomized-double-blind-placebo-controlled-parallel-group-multi-center-study-of-the-safety-and-efficacy-of-adam-zolmitriptan-for-the-acute-treatment-of-migraine
#3
Egilius Lh Spierings, Jan Lewis Brandes, David B Kudrow, James Weintraub, Peter C Schmidt, Donald J Kellerman, Stewart J Tepper
Objective To determine the efficacy, tolerability, and safety of ascending doses of Adhesive Dermally-Applied Microarray (ADAM) zolmitriptan versus placebo for acute migraine treatment. Background ADAM is a novel patient-administered system for intracutaneous drug administration. In a phase 1 pharmacokinetic study, zolmitriptan administered using ADAM had much faster absorption than oral administration with higher exposure in the first two hours. Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 2b/3 study evaluating ADAM zolmitriptan 1 mg, 1...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28993339/the-alternative-sigma-factors-sige-and-sigb-are-involved-in-tolerance-and-persistence-to-antitubercular-drugs
#4
Davide Pisu, Roberta Provvedi, Dulce Mata Espinosa, Jorge Barrios Payan, Francesca Boldrin, Giorgio Palù, Rogelio Hernandez-Pando, Riccardo Manganelli
Emergence and spread of drug resistant Mycobacterium tuberculosis strains threatens our ability the possibility to treat this disease in the future. Even if two new antitubercular drugs were recently introduced, there is still the need to design new molecules whose mechanism of action could reduce treatment length. We showed that two alternative sigma factors of M. tuberculosis (SigE and SigB) have a major role in determining the level of basal resistance to several drugs and the amount of persisters surviving long drug treatment...
October 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28980112/formation-of-persisters-in-streptococcus-mutans-biofilms-induced-by-antibacterial-dental-monomer
#5
Suping Wang, Chenchen Zhou, Biao Ren, Xiaodong Li, Michael D Weir, Radi M Masri, Thomas W Oates, Lei Cheng, Hockin K H Xu
Antibacterial monomers can combat oral biofilm acids and caries; however, little is known on whether quaternary ammonium monomers (QAMs) would induce drug persistence in oral bacteria. The objectives of this study were to investigate the interactions of Streptococcus mutans (S. mutans) with dimethylaminohexadecyl methacrylate (DMAHDM), and determine for the first time whether DMAHDM could induce persisters in S. mutans. DMAHDM was synthesized using a modified Menschutkin reaction. Dose-dependent killing curves and time-dependent killing curves of planktonic S...
October 4, 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28979262/cd28-blockade-ex-vivo-induces-alloantigen-specific-immune-tolerance-but-preserves-t-cell-pathogen-reactivity
#6
Barbara Dillinger, Sarah Ahmadi-Erber, Klara Soukup, Angela Halfmann, Silke Schrom, Bernard Vanhove, Peter Steinberger, Rene Geyeregger, Stephan Ladisch, Alexander Michael Dohnal
Donor T-cells contribute to reconstitution of protective immunity after allogeneic hematopoietic stem cell transplantation (HSCT) but must acquire specific tolerance against recipient alloantigens to avoid life-threatening graft-versus-host disease (GvHD). Systemic immunosuppressive drugs may abrogate severe GvHD, but this also impedes memory responses to invading pathogens. Here, we tested whether ex vivo blockade of CD28 co-stimulation can enable selective T-cell tolerization to alloantigens by facilitating CD80/86-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28979246/variable-persister-gene-interactions-with-p-ppgpp-for-persister-formation-in-escherichia-coli
#7
Shuang Liu, Nan Wu, Shanshan Zhang, Youhua Yuan, Wenhong Zhang, Ying Zhang
Persisters comprise a group of phenotypically heterogeneous metabolically quiescent bacteria with multidrug tolerance and contribute to the recalcitrance of chronic infections. Although recent work has shown that toxin-antitoxin (TA) system HipAB depends on stringent response effector (p)ppGppin persister formation, whether other persister pathways are also dependent on stringent response has not been explored. Here we examined the relationship of (p)ppGpp with 15 common persister genes (dnaK, clpB, rpoS, pspF, tnaA, sucB, ssrA, smpB, recA, umuD, uvrA, hipA, mqsR, relE, dinJ) using Escherichia coli as a model...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28965939/impaired-intracellular-pathogen-clearance-and-inflammatory-joint-disease-is-whipple-s-disease-a-guiding-light
#8
Jean-Marie Berthelot, Xavier Puéchal
Whipple's disease can mimic spondyloarthritis (SpA) or rheumatoid arthritis (RA) for many years and, in a few cases, induces the development of antibodies to cyclic citrullinated peptides. The causative agent Tropheryma whipplei can smolder within cells, including macrophages, by suppressing the xenophagic process, a type of selective autophagy that targets pathogens. Other inflammatory joint diseases may also stem from impaired xenophagy with persistence of bacteria or viruses that can eventually migrate from the mucous membranes to the joints and entheses, where they may exert adverse effects on immune responses, even if they fail to replicate...
September 28, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28937406/tolerance-in-xenotransplantation
#9
Kazuhiko Yamada, Megan Sykes, David H Sachs
PURPOSE OF REVIEW: This review describes recent progress in tolerance-inducing strategies across xenogeneic immunological barriers as well as the potential benefit of a tolerance strategy for islets and kidney xenotransplantation. RECENT FINDINGS: Using advanced gene editing technologies, xenotransplantation from multitransgenic alpha-1,3-galactosyltransferase knockout pigs has demonstrated marked prolongation of renal xenograft survival, ranging from days to greater than several months for life-supporting kidneys, and more than 2 years in a heterotopic nonlife-supporting cardiac xenograft model...
September 20, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28931433/role-of-gabaa-receptors-in-alcohol-use-disorders-suggested-by-chronic-intermittent-ethanol-cie-rodent-model
#10
REVIEW
Richard W Olsen, Jing Liang
GABAergic inhibitory transmission is involved in the acute and chronic effects of ethanol on the brain and behavior. One-dose ethanol exposure induces transient plastic changes in GABAA receptor subunit levels, composition, and regional and subcellular localization. Rapid down-regulation of early responder δ subunit-containing GABAA receptor subtypes mediating ethanol-sensitive tonic inhibitory currents in critical neuronal circuits corresponds to rapid tolerance to ethanol's behavioral responses. Slightly slower, α1 subunit-containing GABAA receptor subtypes mediating ethanol-insensitive synaptic inhibition are down-regulated, corresponding to tolerance to additional ethanol behaviors plus cross-tolerance to other GABAergic drugs including benzodiazepines, anesthetics, and neurosteroids, especially sedative-hypnotic effects...
September 20, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28926559/novelties-in-evaluation-and-monitoring-of-human-immunodeficiency-virus-1-infection-is-standard-virological-suppression-enough-for-measuring-antiretroviral-treatment-success
#11
Valentina Svicher, Giulia Marchetti, Adrianna Ammassari, Francesca Ceccherini-Silberstein, Loredana Sarmati
The high potency and tolerability of the currently available antiretroviral drugs has modified HIV-1 infection from a life-threatening disease to a chronic illness. Nevertheless, some issues still remain open to optimize the management of HIV-1 infected patients in term of maintenance of virological suppression over time, identifying patients that could benefit from simplification therapy, and reducing co-mordibities driven by chronic inflammation. The availability of robust and affordable virological and immunological markers can help in solving these issues by providing information on the burden of HIV-1 reservoir in all the anatomical compartments in which the virus replicates as well as on persistent inflammation, immune activation and senescence despite successful virological suppression...
September 19, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28922692/phosphodiesterase-4-inhibitors-for-chronic-obstructive-pulmonary-disease
#12
REVIEW
Jimmy Chong, Bonnie Leung, Phillippa Poole
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This is an update of a Cochrane review first published in 2011 and updated in 2013...
September 19, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28915286/treatment-of-rosacea-with-concomitant-use-of-topical-ivermectin-1-cream-and-brimonidine-0-33-gel-a-randomized-vehicle-controlled-study
#13
Linda Stein Gold, Kim Papp, Charles Lynde, Edward Lain, Melinda Gooderham, Sandra Johnson, Nabil Kerrouche
BACKGROUND: There is currently a lack of data on the simultaneous treatment of different features of rosacea. Individually, ivermectin 1% (IVM) cream and brimonidine 0.33% (BR) gel have demonstrated efficacy on inflammatory lesions and persistent erythema, respectively. OBJECTIVE: To evaluate the efficacy, safety, patient satisfaction, and optimal timing of administration of IVM associated with BR (IVM+BR) versus their vehicles in rosacea (investigator global assessment [IGA] ≥3)...
September 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28905255/benefit-risk-profile-of-sphingosine-1-phosphate-receptor-modulators-in-relapsing-and-secondary-progressive-multiple-sclerosis
#14
Giancarlo Comi, Hans-Peter Hartung, Rajesh Bakshi, Ian M Williams, Heinz Wiendl
Since the approval of fingolimod, several selective sphingosine-1-phosphate receptor modulators have entered clinical development for multiple sclerosis. However, side effects can occur with sphingosine-1-phosphate receptor modulators. By considering short-term data across the drug class and longer term fingolimod data, we aim to highlight the potential of sphingosine-1-phosphate receptor modulators in multiple sclerosis, while offering reassurance that their benefit-risk profiles are suitable for long-term therapy...
September 13, 2017: Drugs
https://www.readbyqxmd.com/read/28892721/glial-and-neuroinflammatory-targets-for-treating-substance-use-disorders
#15
REVIEW
Ryan K Bachtell, Jermaine D Jones, Keith G Heinzerling, Patrick M Beardsley, Sandra D Comer
BACKGROUND: The plenary session at the 2016 Behavior, Biology and Chemistry: Translational Research in Addiction Conference focused on glia as potential players in the development, persistence and treatment of substance use disorders. Glia partake in various functions that are important for healthy brain activity. Drugs of abuse alter glial cell activity producing several perturbations in brain function that are thought to contribute to behavioral changes associated with substance use disorders...
August 31, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28844471/remodeling-t-cell-compartments-during-anti-cd3-immunotherapy-of-type-1-diabetes
#16
RANDOMIZED CONTROLLED TRIAL
S Alice Long, Jerill Thorpe, Kevan C Herold, Mario Ehlers, Srinath Sanda, Noha Lim, Peter S Linsley, Gerald T Nepom, Kristina M Harris
The immunological mechanism(s) of action whereby teplizumab preserves C-peptide levels in the progression of patients with recent onset type 1 diabetes (T1D) is still not well understood. In the present study, we evaluated the kinetics of T cell modulation in peripheral blood following two 14-day courses of teplizumab therapy one year apart in recent onset T1D participants in the AbATE clinical trial. Transient rises in PD-1+Foxp3+ Treg and potentially anergic (CD57-KLRG1-PD-1+) cells in the circulating CD4 T cell compartment were paralleled by more profound increases in circulating CD8 T cells with traits of exhaustion (CD57-KLRG1+PD-1+, TIGIT+KLRG1+, and persistent down-modulation of CD127)...
September 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28838808/characterization-of-structurally-novel-g-protein-biased-cb1-agonists-implications-for-drug-development
#17
Benjamin M Ford, Lirit N Franks, Sherrica Tai, William E Fantegrossi, Edward L Stahl, Michael D Berquist, Christian V Cabanlong, Catheryn D Wilson, Narsimha R Penthala, Peter A Crooks, Paul L Prather
The human cannabinoid subtype 1 receptor (hCB1R) is highly expressed in the CNS and serves as a therapeutic target for endogenous ligands as well as plant-derived and synthetic cannabinoids. Unfortunately, acute use of hCB1R agonists produces unwanted psychotropic effects and chronic administration results in development of tolerance and dependence, limiting the potential clinical use of these ligands. Studies in β-arrestin knockout mice suggest that interaction of certain GPCRs, including μ-, δ-, κ-opioid and hCB1Rs, with β-arrestins might be responsible for several adverse effects produced by agonists acting at these receptors...
August 23, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28831550/persistence-to-oral-disease-modifying-therapies-in-multiple-sclerosis-patients
#18
Simona Lattanzi, Maura Danni, Ruja Taffi, Raffaella Cerqua, Giulia Carlini, Alessandra Pulcini, Leandro Provinciali, Mauro Silvestrini
Dimethyl fumarate (DMF), fingolimod (FTY) and teriflunomide (TFN) are oral disease-modifying therapies (DMTs) approved for relapsing-remitting multiple sclerosis (RRMS) whose efficacy and tolerability have been separately assessed in phase III trials. Conversely, little evidence exists about their head-to-head comparison. The aim of the study was to evaluate the 1-year persistence to DMF, FTY and TFN in patients with RRMS. Patients affected by RRMS who started treatment with DMF, FTY or TFN were identified...
August 22, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28829910/oxycodone-for-cancer-related-pain
#19
REVIEW
Mia Schmidt-Hansen, Michael I Bennett, Stephanie Arnold, Nathan Bromham, Jennifer S Hilgart
BACKGROUND: Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well-tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated version of the original Cochrane review published in 2015, Issue 2 on oxycodone for cancer-related pain...
August 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28826742/a-comprehensive-review-and-update-on-crohn-s-disease
#20
Mahesh Gajendran, Priyadarshini Loganathan, Anthony P Catinella, Jana G Hashash
The term inflammatory bowel disease (IBD) refers principally to two major categories of chronic relapsing inflammatory intestinal disorders: Crohn's disease (CD) and ulcerative colitis (UC). In the United States, it is currently estimated that about 1.5 million people suffer from IBD, causing considerable suffering, mortality and economic loss every year. Yet the cause of IBD is unknown, and until we understand more, prevention or cure will not be possible. There is a lot of variation in the incidence and prevalence of CD based on geographic region, environment, immigrant population, and ethnic groups...
August 18, 2017: Disease-a-month: DM
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