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Drug tolerant persister

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https://www.readbyqxmd.com/read/28529326/persistent-bacterial-infections-and-persister-cells
#1
REVIEW
Robert A Fisher, Bridget Gollan, Sophie Helaine
Many bacteria can infect and persist inside their hosts for long periods of time. This can be due to immunosuppression of the host, immune evasion by the pathogen and/or ineffective killing by antibiotics. Bacteria can survive antibiotic treatment if they are resistant or tolerant to a drug. Persisters are a subpopulation of transiently antibiotic-tolerant bacterial cells that are often slow-growing or growth-arrested, and are able to resume growth after a lethal stress. The formation of persister cells establishes phenotypic heterogeneity within a bacterial population and has been hypothesized to be important for increasing the chances of successfully adapting to environmental change...
May 22, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28518128/an-in-vitro-caseum-binding-assay-that-predicts-drug-penetration-in-tuberculosis-lesions
#2
Jansy P Sarathy, Hsin-Pin Ho Liang, Danielle Weiner, Jacqueline Gonzales, Laura E Via, Véronique Dartois
The eradication of tuberculosis disease requires drug regimens that can penetrate the multiple layers of complex pulmonary lesions. Drug distribution in the caseous cores of cavities and lesions is especially crucial because they harbor subpopulations of drug-tolerant bacteria also commonly referred to as persisters. Existing methods for the measurement of drug penetration in tuberculosis lesions involve costly and time-consuming in vivo pharmacokinetic studies coupled to bioanalytical or imaging techniques...
May 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28513455/glucose-tolerance-disorders-during-treatment-with-glucocorticoids-in-patients-with-inflammatory-diseases-of-the-musculoskeletal-system-based-on-the-analysis-of-data-from-the-literature-and-own-research-results
#3
Piotr Dąbrowski, Maria Majdan
Glucocorticoids are among the most frequently used anti-inflammatory and immunosuppressive drugs. They are widely used in the treatment of numerous autoimmune disorders. However, the treatment with glucocorticoids is connected with the risk of a number of side effects. Among them, glucose tolerance disorders play an important role. The results of meta-analyses show that the risk of diabetes is from 1.4 to 2.5 times higher in the case of treated patients in comparison to the general population. Glucocorticoids can directly impair pancreatic β-cell secretion...
May 4, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28510695/effects-of-an-autoinducer-analogue-on-antibiotic-tolerance-in-pseudomonas-aeruginosa
#4
Takashi Amoh, Keiji Murakami, Reiko Kariyama, Kenji Hori, Darija Viducic, Katsuhiko Hirota, Jun Igarashi, Hiroaki Suga, Matthew R Parsek, Hiromi Kumon, Yoichiro Miyake
Objectives: Antibiotic tolerance causes chronic, refractory and persistent infections. In order to advance the development of a new type of drug for the treatment of infectious diseases, we herein investigated the effects of a newly synthesized analogue of the Pseudomonas aeruginosa quorum-sensing autoinducer named AIA-1 ( a uto i nducer a nalogue) on antibiotic tolerance in P. aeruginosa . Methods: A P. aeruginosa luminescent strain derived from PAO1 was injected into neutropenic ICR mice and bioluminescence images were acquired for a period of time after treatments with antibiotics and AIA-1...
May 16, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28495642/feasibility-of-lenalidomide-therapy-for-persistent-chronic-lymphocytic-leukemia-after-allogeneic-transplantation
#5
Maria R Khouri, Elias J Jabbour, Alison M Gulbis, Francesco Turturro, Celina Ledesma, Martin Korbling, Barry I Samuels, Sairah Ahmed, Amin M Alousi, Stefan O Ciurea, David Marin, Krina K Patel, Uday R Popat, Carlos E Bueso-Ramos, Roland L Bassett, Issa F Khouri
In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90-100 days post alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily if tolerated in each patient...
May 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28484041/transcriptional-repressor-ptvr-regulates-phenotypic-tolerance-to-vancomycin-in-streptococcus-pneumoniae
#6
Xue Liu, Jing-Wen Li, Zhixing Feng, Youfu Luo, Jan-Willem Veening, Jing-Ren Zhang
Reversible or phenotypic tolerance to antibiotics within microbial populations has been implicated in treatment failure of chronic infections and development of persister cells. However, the molecular mechanisms regulating phenotypic drug tolerance are largely unknown. In this study, we identified a four-gene operon in Streptococcus pneumoniae that contributes to phenotypic tolerance to vancomycin (ptv). RNA-Seq, qRT-PCR, and transcriptional luciferase reporter experiments revealed that transcription of the ptv operon (consisting of ptvR, ptvA, ptvB and ptvC) is induced by exposure to vancomycin...
May 8, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28473458/effects-of-acute-and-chronic-treatments-with-d2-and-d3-receptor-ligands-on-cocaine-vs-food-choice-in-rats
#7
Morgane Thomsen, Andrew C Barrett, Paul Butler, S Stevens Negus, S Barak Caine
Dopamine D3 receptor ligands are potential medications for psychostimulant addiction. Medication assessment may benefit from preclinical studies that evaluate chronic medication effects on choice between an abused drug and an alternative, non-drug reinforcer. This study compared acute and chronic effects of dopamine D2- and D3-preferring ligands on choice between intravenous cocaine and palatable food in rats. Under baseline conditions, cocaine maintained dose-dependent increases in cocaine choice and reciprocal decreases in food choice...
May 4, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28461784/retrospective-evaluation-of-the-effectiveness-of-radiotherapy-in-patients-with-plantar-fascitis-heel-spurs
#8
Piotr Kędzierawski, Rafał Stando, Paweł Macek
AIM: The aim of the study was the evaluation of the effectiveness of radiotherapy in patients with the feet pain caused by heel spurs. BACKGROUND: Treatment options for patients reporting these symptoms include use of suitable orthopedic footwear, the use of general or topical non-steroidal anti-inflammatory drugs or steroids, physiotherapy, manual therapy, shock wave or appropriate surgical procedures. Radiotherapy is one of the method used in patients with chronic pain syndrome...
May 2017: Reports of Practical Oncology and Radiotherapy
https://www.readbyqxmd.com/read/28458514/riociguat-a-soluble-guanylate-cyclase-stimulator-for-the-treatment-of-pulmonary-hypertension
#9
REVIEW
Tian-Yu Lian, Xin Jiang, Zhi-Cheng Jing
Despite advances in treatments and improved survival, patients with pulmonary hypertension still experience poor exercise and functional capacity, which has a significant detrimental impact on their quality of life. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine 3',5'-monophosphate (cGMP) pathway has been shown to play an important role in cardiovascular physiology, especially in vasodilation and pulmonary vascular tone. The oral sGC stimulator riociguat has a dual mode of action on the NO-sGC-cGMP pathway: direct stimulation of sGC independent of NO and indirect simulation via sensitization of sGC to endogenous NO...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28450388/clinical-relevance-of-detecting-anti-infliximab-antibodies-with-a-drug-tolerant-assay-post-hoc-analysis-of-the-taxit-trial
#10
Thomas Van Stappen, Niels Vande Casteele, Gert Van Assche, Marc Ferrante, Séverine Vermeire, Ann Gils
OBJECTIVE: To evaluate the clinical relevance of antidrug antibodies (ADAs) measured using a drug-tolerant assay in a post hoc analysis of the Trough Concentration (TC) Adapted Infliximab Treatment (TAXIT) randomised controlled trial. DESIGN: ADA in serum samples (n=221) of 76 patients enrolled in TAXIT, who presented with an infliximab TC <3 µg/mL at screening, were reanalysed after optimisation and at the end of the study using a drug-tolerant ADA assay...
April 27, 2017: Gut
https://www.readbyqxmd.com/read/28445002/glucose-metabolism-targeting-therapy-and-withaferin-a-are-effective-for-egfr-tki-induced-drug-tolerant-persisters
#11
Kei Kunimasa, Tatsuya Nagano, Yohei Shimono, Ryota Dokuni, Tatsunori Kiriu, Shuntaro Tokunaga, Daisuke Tamura, Masatsugu Yamamoto, Motoko Tachihara, Kazuyuki Kobayashi, Miyako Satouchi, Yoshihiro Nishimura
In pathway-targeted cancer drug therapies, the relatively rapid emergence of drug-tolerant persisters (DTPs) substantially limits the overall therapeutic benefit. However, little is known about the roles of DTPs in drug resistance. In this study, we investigated the features of EGFR-TKI induced DTPs and explored a new treatment strategy to overcome the emergence of these DTPs. We used two EGFR mutated lung adenocarcinoma cell lines, PC9 and II-18. They were treated with 2 μM gefitinib for 6, 12, or 24 days or 6 month...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28435338/recommendations-for-optimizing-methotrexate-treatment-for-patients-with-rheumatoid-arthritis
#12
REVIEW
Alfonso E Bello, Elizabeth L Perkins, Randy Jay, Petros Efthimiou
Methotrexate (MTX) remains the cornerstone therapy for patients with rheumatoid arthritis (RA), with well-established safety and efficacy profiles and support in international guidelines. Clinical and radiologic results indicate benefits of MTX monotherapy and combination with other agents, yet patients may not receive optimal dosing, duration, or route of administration to maximize their response to this drug. This review highlights best practices for MTX use in RA patients. First, to improve the response to oral MTX, a high initial dose should be administered followed by rapid titration...
2017: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/28431060/catheter-ablation-vs-antiarrhythmic-drug-therapy-in-patients-with-symptomatic-atrioventricular-nodal-re-entrant-tachycardia-a-randomized-controlled-trial
#13
Demosthenes G Katritsis, Theodoros Zografos, George D Katritsis, Eleftherios Giazitzoglou, Vasilios Vachliotis, George Paxinos, A John Camm, Mark E Josephson
Aims: To conduct a randomized trial in order to guide the optimum therapy of symptomatic atrioventricular nodal re-entrant tachycardia (AVNRT). Methods and Results: Patients with at least one symptomatic episode of tachycardia per month and an electrophysiologic diagnosis of AVNRT were randomly assigned to catheter ablation or chronic antiarrhythmic drug (AAD) therapy with bisoprolol (5 mg od) and/or diltiazem (120-300 mg od). All patients were properly educated to treat subsequent tachycardia episodes with autonomic manoeuvres or a 'pill in the pocket' approach...
April 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28405132/antianginal-efficacy-and-tolerability-of-ranolazine-as-an-add-on-drug-to-concomitant-medications-primarily-metoprolol-in-chronic-stable-angina-patients-a-prospective-open-label-study
#14
Anant Mahaveer Khot, H V Anuradha, V S Prakash, M C Shivamurathy
OBJECTIVE: To evaluate the efficacy and tolerability of ranolazine as an add-on drug in chronic stable angina patients and the impact of ranolazine on the quality of life in chronic stable angina patients receiving other antianginal medications. MATERIALS AND METHODS: It was a prospective, open-label, hospital-based study involving 144 patients with chronic stable angina. First group received either metoprolol 12.5 or 25 mg/day or other antianginal medications; if the symptoms persist, the dose of metoprolol was increased to 50 mg/day, and to the second group, ranolazine 500 mg BD or 1 g OD was added along with metoprolol or others if the anginal attacks were not subsiding...
January 2017: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/28396391/enhanced-respiration-prevents-drug-tolerance-and-drug-resistance-in-mycobacterium-tuberculosis
#15
Catherine Vilchèze, Travis Hartman, Brian Weinrick, Paras Jain, Torin R Weisbrod, Lawrence W Leung, Joel S Freundlich, William R Jacobs
Persistence, manifested as drug tolerance, represents a significant obstacle to global tuberculosis control. The bactericidal drugs isoniazid and rifampicin kill greater than 99% of exponentially growing Mycobacterium tuberculosis (Mtb) cells, but the remaining cells are persisters, cells with decreased metabolic rate, refractory to killing by these drugs, and able to generate drug-resistant mutants. We discovered that the combination of cysteine or other small thiols with either isoniazid or rifampicin prevents the formation of drug-tolerant and drug-resistant cells in Mtb cultures...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28363336/active-efflux-in-dormant-bacterial-cells-new-insights-into-antibiotic-persistence
#16
Yingying Pu, Yuehua Ke, Fan Bai
Bacterial persisters are phenotypic variants of an isogenic cell population that can survive antibiotic treatment and resume growth after the antibiotics have been removed. Cell dormancy has long been considered the principle mechanism underlying persister formation. However, dormancy alone is insufficient to explain the full range of bacterial persistence. Our recent work revealed that in addition to 'passive defense' via dormancy, persister cells employ 'active defense' via enhanced efflux activity to expel drugs...
January 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/28361736/dna-replication-in-mycobacterium-tuberculosis
#17
Zanele Ditse, Meindert H Lamers, Digby F Warner
Faithful replication and maintenance of the genome are essential to the ability of any organism to survive and propagate. For an obligate pathogen such as Mycobacterium tuberculosis that has to complete successive cycles of transmission, infection, and disease in order to retain a foothold in the human population, this requires that genome replication and maintenance must be accomplished under the metabolic, immune, and antibiotic stresses encountered during passage through variable host environments. Comparative genomic analyses have established that chromosomal mutations enable M...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28349350/visual-snow-a-potential-cortical-hyperexcitability-syndrome
#18
REVIEW
Alaa Bou Ghannam, Victoria S Pelak
The purpose of this review is to provide an overview of visual snow (VS) and provide information regarding current treatment options for VS. Visual snow (VS) is a rare disorder manifesting with a persistent visual phenomenon of seeing numerous tiny snow-like dots throughout the visual field, and it can cause debilitating visual and psychological consequences. It is emerging as a disorder separate from, but associated with, migraine visual aura, and neuronal cortical hyperexcitability is being considered as a theoretical mechanism for the persistent-positive visual symptoms...
March 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28292795/primary-care-management-of-opioid-use-disorders-abstinence-methadone-or-buprenorphine-naloxone
#19
REVIEW
Anita Srivastava, Meldon Kahan, Maya Nader
OBJECTIVE: To advise physicians on which treatment options to recommend for specific patient populations: abstinence-based treatment, buprenorphine-naloxone maintenance, or methadone maintenance. SOURCES OF INFORMATION: PubMed was searched and literature was reviewed on the effectiveness, safety, and side effect profiles of abstinence-based treatment, buprenorphine-naloxone treatment, and methadone treatment. Both observational and interventional studies were included...
March 2017: Canadian Family Physician Médecin de Famille Canadien
https://www.readbyqxmd.com/read/28291085/respiratory-effects-of-the-nociceptin-orphanin-fq-peptide-and-opioid-receptor-agonist-cebranopadol-in-healthy-human-volunteers
#20
Albert Dahan, Merel Boom, Elise Sarton, Justin Hay, Geert Jan Groeneveld, Meike Neukirchen, John Bothmer, Leon Aarts, Erik Olofsen
BACKGROUND: Cebranopadol is a novel strong analgesic that coactivates the nociceptin/orphanin FQ receptor and classical opioid receptors. There are indications that activation of the nociceptin/orphanin FQ receptor is related to ceiling in respiratory depression. In this phase 1 clinical trial, we performed a pharmacokinetic-pharmacodynamic study to quantify cebranopadol's respiratory effects. METHODS: Twelve healthy male volunteers received 600 μg oral cebranopadol as a single dose...
April 2017: Anesthesiology
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