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Drug tolerant persister

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https://www.readbyqxmd.com/read/29203575/chronic-%C3%AE-9-thc-in-rhesus-monkeys-effects-on-cognitive-performance-and-dopamine-d2-d3-receptor-availability
#1
William S John, Thomas J Martin, Kiran K Solingapuram Sai, Susan H Nader, H D Gage, Akiva Mintz, Michael A Nader
Cannabis-related impairments to cognitive function may represent novel therapeutic targets for cannabis-use disorder, although the nature, persistence, and reversibility of those deficits remain unclear. Adult male rhesus monkeys (N=6) responded in the mornings on tasks designed to assess different cognitive domains using CANTAB touchscreens followed by responding maintained under a fixed-ratio (FR) 10 schedule of food presentation in different operant chambers. First, the acute effects of Δ9-tetrahydrocannabinol (THC; 0...
December 4, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29203492/extreme-drug-tolerance-of-mycobacterium-tuberculosis-in-caseum
#2
Jansy P Sarathy, Laura E Via, Danielle Weiner, Landry Blanc, Helena Boshoff, Eliseo A Eugenin, Clifton E Barry, Véronique A Dartois
Tuberculosis (TB) recently became the leading infectious cause of death in adults, while attempts to shorten therapy have largely failed. Dormancy, persistence and drug tolerance are among the factors driving the long therapy duration. Assays to measure in situ drug susceptibility of Mycobacterium tuberculosis (Mtb) bacteria in pulmonary lesions are needed if we are to discover new fast acting regimens and address the global TB threat. Here we take a first step towards this goal and describe an ex vivo assay developed to measure the cidal activity of anti-TB drugs against Mtb bacilli present in cavity caseum, obtained from rabbits with active TB...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29163329/dystonic-dysarthria-in-wilson-disease-efficacy-of-zolpidem
#3
Aurélia Poujois, Michaela Pernon, Jean-Marc Trocello, France Woimant
Wilson disease (WD) is a rare genetic disorder characterized by copper overload in the liver and the brain. Neurological presentations are mainly related to the accumulation of copper in the basal ganglia, the brainstem, and the cerebellum. Dysarthria is a frequent symptom, with dystonic, spastic, or parkinsonian components and is usually resistant to medical or voice rehabilitation therapies. Here, we report the case of a patient with WD diagnosed at the age of 12, who presented a severe and constant dysarthria from dystonic origin which was unresponsive to benzodiazepines and anticholinergic drugs...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29145012/the-gut-brain-interaction-in-opioid-tolerance
#4
REVIEW
Hamid I Akbarali, William L Dewey
The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms...
November 13, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29143876/deregulation-of-genes-associated-with-alternate-drug-resistance-mechanisms-in-mycobacterium-tuberculosis
#5
Kalpana Sriraman, Kayzad Nilgiriwala, Dhananjaya Saranath, Anirvan Chatterjee, Nerges Mistry
Alternate mechanisms of drug resistance involving intrinsic defense pathways play an important role in development of drug resistance. Deregulation of drug efflux, cellular metabolism, and DNA repair have been indicated to have effect on drug tolerance and persistence. Here we chose eight genes from these pathways to investigate their association with development of multidrug resistance (MDR). We generated mono drug resistant and MDR strains of rifampicin and isoniazid and examined the differential expression of genes belonging to efflux, DNA repair and cell wall lipid synthesis pathways...
November 16, 2017: Current Microbiology
https://www.readbyqxmd.com/read/29141762/efficacy-of-artemether-lumefantrine-for-uncomplicated-plasmodium-falciparum-malaria-in-cruzeiro-do-sul-brazil-2016
#6
Megumi Itoh, Suiane Negreiros do Valle, Sâmela Farias, Thayna Maria Holanda de Souza, Giselle Maria Rachid Viana, Naomi Lucchi, Stella Chenet, Paola Marchesini, Marinete Póvoa, Ana Carolina Faria E Silva Santelli, Alexandre Macedo de Oliveira
We evaluated the therapeutic efficacy of artemether-lumefantrine (AL) fixed-dose combination to treat uncomplicated Plasmodium falciparum malaria in Cruzeiro do Sul, Acre State, in the Amazon region of Brazil. Between December 2015 and May 2016, we enrolled 79 patients, 5-79 years old with fever or history of fever in the previous 48 hours and P. falciparum monoinfection confirmed by microscopy. Attempts were made to provide direct observation or phone reminders for all six doses of AL, and patients were followed-up for 28 days...
November 6, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29136640/long-term-outcomes-of-the-atypical-hemolytic-uremic-syndrome-after-kidney-transplantation-treated-with-eculizumab-as-first-choice
#7
Luis Gustavo Modelli de Andrade, Mariana Moraes Contti, Hong Si Nga, Ariane Moyses Bravin, Henrique Mochida Takase, Rosa Marlene Viero, Trycia Nunes da Silva, Kelem De Nardi Chagas, Lilian Monteiro Pereira Palma
INTRODUCTION: The treatment of choice for Atypical Hemolytic Uremic Syndrome (aHUS) is the monoclonal antibody eculizumab. The objective of this study was to assess the efficacy and safety of eculizumab in a cohort of kidney transplant patients suffering from aHUS. METHODS: Description of the prospective cohort of all the patients primarily treated with eculizumab after transplantation and divided into the therapeutic (onset of aHUS after transplantation) and prophylactic use (patients with previous diagnosis of aHUS undergoing kidney transplantation)...
2017: PloS One
https://www.readbyqxmd.com/read/29127085/gpx4-inhibition-selectively-targets-drug-tolerant-persister-cells
#8
(no author information available yet)
Targeting GPX4 induces selective cell death of drug-tolerant persister tumor cells by ferroptosis.
November 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29096596/comparison-of-the-local-tolerability-to-5-long-acting-drug-nanosuspensions-with-different-stabilizing-excipients-following-a-single-intramuscular-administration-in-the-rat
#9
Ronnie Chamanza, Nicolas Darville, Marjolein van Heerden, Sandra De Jonghe
To investigate the effects of common nanosuspension-stabilizing excipients on the nature and temporal evolution of histopathological changes at intramuscular (i.m.) administration sites, 5 groups of 39 male rats per group received a single injection of 1 of the 5 analogous crystalline drug nanosuspensions containing 200 mg/ml of an antiviral compound with particle sizes of ±200 nm and identical vehicle compositions, except for the type of nanosuspension stabilizer. The investigated stabilizers were poloxamer 338, poloxamer 407, d-α-tocopherol polyethylene glycol 1,000-succinate (TPGS), polysorbate 80, and polysorbate 80 combined with egg phosphatidylglycerol...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29095667/pcsk9-inhibitors-mechanisms-of-action-metabolic-effects-and-clinical-outcomes
#10
Connie N Hess, Cecilia C Low Wang, William R Hiatt
Atherosclerotic cardiovascular disease (ASCVD) is associated with significant morbidity and mortality worldwide. Increased serum levels of lowdensity lipoprotein cholesterol (LDL-C) are an independent risk factor for ASCVD, and clinical trial data have shown that lowering LDL-C generally reduces cardiovascular risk. Until recently, 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors (statins) have been the main therapy for lowering LDL-C. However, some statin-treated patients have persistently elevated residual cardiovascular risk due to inadequate lowering of LDL-C levels or non-LDL-related dyslipidemia...
November 2, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/29054992/suppression-of-adaptive-responses-to-targeted-cancer-therapy-by-transcriptional-repression
#11
Maria Rusan, Kapsok Li, Yvonne Li, Camilla L Christensen, Brian J Abraham, Nicholas Kwiatkowski, Kevin A Buczkowski, Bruno Bockorny, Ting Chen, Shuai Li, Kevin Rhee, Haikuo Zhang, Wankun Chen, Hideki Terai, Tiffany Tavares, Alan L Leggett, Tianxia Li, Yichen Wang, Tinghu Zhang, Tae-Jung Kim, Sook-Hee Hong, Neermala Poudel-Neupane, Michael Silkes, Tenny Mudianto, Li Tan, Takeshi Shimamura, Matthew Meyerson, Adam J Bass, Hideo Watanabe, Nathanael S Gray, Richard A Young, Kwok-Kin Wong, Peter S Hammerman
Acquired drug resistance is a major factor limiting the effectiveness of targeted cancer therapies. Targeting tumors with kinase inhibitors induces complex adaptive programs that promote the persistence of a fraction of the original cell population, facilitating the eventual outgrowth of inhibitor-resistant tumor clones. We show that the addition of a newly identified CDK7/12 inhibitor, THZ1, to targeted therapy enhances cell killing and impedes the emergence of drug-resistant cell populations in diverse cellular and in vivo cancer models...
October 20, 2017: Cancer Discovery
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
December 2017: Current Opinion in Organ Transplantation
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