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Drug tolerant persister

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https://www.readbyqxmd.com/read/27924636/safety-and-tolerability-of-glucagon-like-peptide-1-receptor-agonists-unresolved-and-emerging-issues
#1
Denis Raccah
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a mainstay of treatment options for Type 2 diabetes. They contribute to lowering blood glucose levels, generally have a favorable tolerability profile, and can be used alone or in combination with other antidiabetic agents. Based on the duration of their effects, GLP-1 RAs can be divided into two classes: short-acting and long-acting. Differences exist between these sub-classes, and between each drug, in terms of pharmacokinetic and pharmacodynamic profiles...
December 7, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27921270/halogenated-indoles-eradicate-bacterial-persister-cells-and-biofilms
#2
Jin-Hyung Lee, Yong-Guy Kim, Giyeon Gwon, Thomas K Wood, Jintae Lee
The emergence of antibiotic resistance has necessitated new therapeutic approaches to combat recalcitrant bacterial infections. Persister cells, often found in biofilms, are metabolically dormant, and thus, are highly tolerant to all traditional antibiotics and represent a major drug resistance mechanism. In the present study, 36 diverse indole derivatives were investigated with the aim of identifying novel compounds that inhibit persisters and biofilm formation by Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus...
December 2016: AMB Express
https://www.readbyqxmd.com/read/27914754/antiparasitic-and-disease-modifying-activity-of-nyctanthes-arbor-tristis-linn-in-malaria-an-exploratory-clinical-study
#3
Chhaya S Godse, Prakash S Tathed, Sameer S Talwalkar, Rama A Vaidya, Ashok J Amonkar, Akhil B Vaidya, Ashok D B Vaidya
BACKGROUND: An unceasing threat of drug resistance continuously poses demand for new antimalarial drugs. A scientific assessment of traditionally used antimalarial plants through reverse pharmacology is crucial for a fast track drug discovery. An Ayurvedic plant Nyctanthesarbor-tristis Linn. - (Parijat) had shown antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical study. OBJECTIVE: To further explore antimalarial potential of the plant through additional objective markers...
November 30, 2016: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/27912845/molecular-mechanisms-and-clinical-implications-of-bacterial-persistence
#4
Joran Elie Michiels, Bram Van den Bergh, Natalie Verstraeten, Jan Michiels
Any bacterial population harbors a small number of phenotypic variants that survive exposure to high concentrations of antibiotic. Importantly, these so-called 'persister cells' compromise successful antibiotic therapy of bacterial infections and are thought to contribute to the development of antibiotic resistance. Intriguingly, drug-tolerant persisters have also been identified as a factor underlying failure of chemotherapy in tumor cell populations. Recent studies have begun to unravel the complex molecular mechanisms underlying persister formation and revolve around stress responses and toxin-antitoxin modules...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27901275/peripheral-nerve-blocks-for-the-treatment-of-headache-in-older-adults-a-retrospective-study
#5
Jacob R Hascalovici, Matthew S Robbins
OBJECTIVE: The objective of this study is to provide demographical and clinical descriptions of patients age 65 years old and older who were treated with peripheral nerve blocks (PNBs) at our institution and evaluate the safety and efficacy of this treatment. BACKGROUND: Headache disorders are common, disabling chronic neurological diseases that often persist with advancing age. Geriatric headache management poses unique therapeutic challenges because of considerations of comorbidity, drug interactions, and adverse effects...
November 30, 2016: Headache
https://www.readbyqxmd.com/read/27895008/de-novo-emergence-of-genetically-resistant-mutants-of-mycobacterium-tuberculosis-from-the-persistence-phase-cells-formed-against-antituberculosis-drugs-in-vitro
#6
Jees Sebastian, Sharmada Swaminath, Rashmi Ravindran Nair, Kishor Jakkala, Atul Pradhan, Parthasarathi Ajitkumar
Bacterial persisters are a subpopulation of cells that can tolerate lethal concentrations of antibiotics. However, the possibility of the emergence of genetically resistant mutants from antibiotic persister cell population, upon continued exposure to lethal concentrations of antibiotics, remained unexplored. In the present study, we found that Mycobacterium tuberculosis (Mtb) cells exposed continuously to lethal concentrations of rifampicin (RIF) or moxifloxacin (MXF) for prolonged durations showed killing, RIF/MXF persistence, and regrowth phases...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27890790/efficacy-and-tolerability-of-an-ifn-free-regimen-with-dcv-asv-for-elderly-patients-infected-with-hcv-genotype-1b
#7
Hidenori Toyoda, Takashi Kumada, Toshifumi Tada, Noritomo Shimada, Koichi Takaguchi, Tomonori Senoh, Kunihiko Tsuji, Yoshihiko Tachi, Atsushi Hiraoka, Toru Ishikawa, Toshihide Shima, Takeshi Okanoue
BACKGROUND & AIMS: Anti-hepatitis C virus (HCV) therapy by interferon (IFN)-free regimen with oral direct-acting antiviral drugs are tolerable in aged patients, with fewer adverse effects than IFN-based therapies. We investigated the efficacy and tolerability of an IFN-free anti-HCV therapy in extremely aged patients, as well as the survival benefit of sustained virologic response (SVR). METHODS: Following IFN-free therapy with daclatasvir and asunaprevir, tolerability and SVR rate were compared between 115 HCV genotype 1-infected patients aged 80 years or older, 151 patients in their seventies (⩾70 and <80 years), and 115 patients under age 70...
November 24, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27861363/efficacy-safety-and-tolerability-of-a-24-month-treatment-regimen-including-delamanid-in-a-child-with-extensively-drug-resistant-tuberculosis-a-case-report-and-review-of-the-literature
#8
Susanna Esposito, Samantha Bosis, Marina Tadolini, Sonia Bianchini, Giovanni Battista Migliori, Nicola Principi
RATIONAL: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are emerging problems in several countries. These infections require long and expensive treatment regimens. Recently, 2 new drugs, bedaquiline and delamanid, have been approved in several countries for use in adults with severe, difficult-to-treat MDR-TB, and it has been suggested that they could also be administered to children with MDR-TB and limited treatment options. However, no study has been completed on their efficacy...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27830376/clinical-effectiveness-of-itraconazole-as-antifungal-prophylaxis-in-aml-patients-undergoing-intensive-chemotherapy-in-the-modern-era
#9
C L Keighley, P Manii, S R Larsen, S van Hal
Antifungal prophylaxis regimens vary between centres, informed by local epidemiology and antifungal stewardship practices. The advantages of itraconazole over posaconazole prophylaxis include maintaining the utility of azole therapy for suspected breakthrough invasive fungal infection (bIFI). We examined the effectiveness and tolerability of itraconazole as prophylaxis in acute myeloid leukaemia (AML) patients. We sought to determine the rate of probable and proven bIFI in the context of itraconazole prophylaxis in a real-life setting...
November 9, 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27826950/effects-of-common-anesthetic-agents-on-18-f-flumazenil-binding-to-the-gabaa-receptor
#10
Mikael Palner, Corinne Beinat, Sam Banister, Francesca Zanderigo, Jun Hyung Park, Bin Shen, Trine Hjoernevik, Jae Ho Jung, Byung Chul Lee, Sang Eun Kim, Lawrence Fung, Frederick T Chin
BACKGROUND: The availability of GABAA receptor binding sites in the brain can be assessed by positron emission tomography (PET) using the radioligand, [(18)F]flumazenil. However, the brain uptake and binding of this PET radioligand are influenced by anesthetic drugs, which are typically needed in preclinical imaging studies and clinical imaging studies involving patient populations that do not tolerate relatively longer scan times. The objective of this study was to examine the effects of anesthesia on the binding of [(18)F]flumazenil to GABAA receptors in mice...
December 2016: EJNMMI Research
https://www.readbyqxmd.com/read/27823963/new-approaches-to-antimicrobial-discovery
#11
REVIEW
Kim Lewis
The spread of resistant organisms is producing a human health crisis, as we are witnessing the emergence of pathogens resistant to all available antibiotics. An increase in chronic infections presents an additional challenge - these diseases are difficult to treat due to antibiotic-tolerant persister cells. vermining of soil Actinomycetes ended the golden era of antibiotic discovery in the 60s, and efforts to replace this source by screening synthetic compound libraries was not successful. Bacteria have an efficient permeability barrier, preventing penetration of most synthetic compounds...
November 4, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27822201/a-tolc-like-protein-of-actinobacillus-pleuropneumoniae-is-involved-in-antibiotic-resistance-and-biofilm-formation
#12
Ying Li, Sanjie Cao, Luhua Zhang, Gee W Lau, Yiping Wen, Rui Wu, Qin Zhao, Xiaobo Huang, Qigui Yan, Yong Huang, Xintian Wen
Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, a significant disease that causes serious economic losses to the swine industry worldwide. Persistent infections caused by bacterial biofilms are recalcitrant to treat because of the particular drug resistance of biofilm-dwelling cells. TolC, a key component of multidrug efflux pumps, are responsible for multidrug resistance (MDR) in many Gram-negative bacteria. In this study, we identified two TolC-like proteins, TolC1 and TolC2, in A...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27822048/analysis-of-treatment-patterns-and-persistence-on-branded-and-generic-medications-in-major-depressive-disorder-using-retrospective-claims-data
#13
Caitlyn T Solem, Ahmed Shelbaya, Yin Wan, Chinmay G Deshpande, Jose Alvir, Elizabeth Pappadopulos
BACKGROUND: In major depressive disorder (MDD), treatment persistence is critical to optimize symptom remission, functional recovery, and health care costs. Desvenlafaxine tends to have fewer drug interactions and better tolerability than other MDD drugs; however, its use has not been assessed in the real world. OBJECTIVE: The aim of the present study is to compare medication persistence and concomitant MDD drug use with branded desvenlafaxine (Pristiq(®)) compared with antidepressant drug groups classified as 1) branded selective serotonin reuptake inhibitors (SSRIs; ie, escitalopram [Lexapro™]) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs; ie, venlafaxine [Effexor(®)], duloxetine [Cymbalta(®)]) and 2) generic SSRIs/SNRIs (ie, escitalopram, citalopram, venlafaxine, fluvoxamine, fluoxetine, sertraline, paroxetine, and duloxetine)...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27819156/development-of-a-qualitative-qpcr-test-to-identify-patients-failing-first-time-therapy-to-nnrti
#14
Sergio Lisboa Machado, Gabriel S Gonçalves, Dawn Dudley, David O'Connor, Helena Keiko Toma, José C Couto-Fernandez, Amilcar Tanuri
Antiretroviral therapy (ART) can be compromised by selection of drug-resistance strains; this can be promoted by lack of adherence during therapy and drug tolerability. Some of these drug resistant strains can persist for years as minority populations. The K103N drug resistance mutation (DRM) is selected by the use of NNRTIs including Nevirapine or Efavirenz that are used in low-income countries. Here we describe the use of a less expensive qualitative Point Mutation PCR (PMqPCRK103N) targeting K103N mutation...
November 7, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27802969/ibrutinib-efficacy-and-tolerability-in-patients-with-relapsed-chronic-lymphocytic-leukemia-following-allogeneic-hct
#15
Christine E Ryan, Bita Sahaf, Aaron C Logan, Susan O'Brien, John C Byrd, Peter Hillmen, Jennifer R Brown, Martin J S Dyer, Anthony R Mato, Michael J Keating, Samantha Jaglowski, Fong Clow, Andrew R Rezvani, Lori Styles, Steven E Coutre, David B Miklos
Ibrutinib, a potent and irreversible small molecule inhibitor of both Bruton's tyrosine kinase (BTK) and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival. Here we present 27 patients with relapsed CLL following allogeneic hematopoietic cell transplantation who subsequently received ibrutinib salvage therapy. Sixteen of these patients were part of multi-institutional clinical trials and achieved an overall response rate of 87...
November 1, 2016: Blood
https://www.readbyqxmd.com/read/27797970/molecular-pathways-maintaining-mapk-inhibitor-sensitivity-by-targeting-nonmutational-tolerance
#16
Michael P Smith, Claudia Wellbrock
Targeting hyperactive MAPK signaling has proven to be an effective treatment for a variety of different cancers. Responses to the BRAF inhibitors vemurafenib and dabrafenib and the MEK inhibitors trametinib and cobimetinib are, however, transient, and complete remission is rarely observed; rather, outgrowth of resistant clones within progressed tumors appears inevitable. These resistant tumors display great heterogeneity, which poses a major challenge to any salvage therapy. Recent focus has, therefore, been on the early dynamics of inhibitor response during tumor regression...
October 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27795412/design-and-in-vivo-characterization-of-immunoconjugates-targeting-hiv-gp160
#17
Seth H Pincus, Kejing Song, Grace A Maresh, Anderson Frank, David Worthylake, Hye-Kyung Chung, Patricia Polacino, Dean H Hamer, Cody P Coyne, Michael G Rosenblum, John W Marks, Gang Chen, Deborah Weiss, Victor Ghetie, Ellen S Vitetta, James E Robinson, Shiu-Lok Hu
: The envelope (Env) glycoprotein of HIV is expressed on the surface of productively-infected cells, and can be used as a target for cytotoxic immunoconjugates (ICs), in which cell-killing moieties including toxins, drugs, or radionuclides are chemically or genetically linked to monoclonal antibodies (MAbs) or other targeting ligands. Such ICs could be used to eliminate persistent reservoirs of HIV infection. We have found that MAbs which bind to the external loop of gp41, e.g MAb 7B2, make highly effective ICs, particularly when used in combination with soluble CD4...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27780992/epigenetic-modifications-alcoholic-brain-and-potential-drug-targets
#18
REVIEW
Ashok Jangra, Chandra Shaker Sriram, Suryanarayan Pandey, Priyansha Choubey, Prabha Rajput, Babita Saroha, Babul Kumar Bezbaruah, Mangala Lahkar
Acute and chronic alcohol exposure evidently influences epigenetic changes, both transiently and permanently, and these changes in turn influence a variety of cells and organ systems throughout the body. Many of the alcohol-induced epigenetic modifications can contribute to cellular adaptations that ultimately lead to behavioral tolerance and alcohol dependence. The persistence of behavioral changes demonstrates that long-lasting changes in gene expression, within particular regions of the brain, may contribute importantly to the addiction phenotype...
October 2016: Annals of Neurosciences
https://www.readbyqxmd.com/read/27757016/a-fixed-dose-combination-of-memantine-extended-release-and-donepezil-in-the-treatment-of-moderate-to-severe-alzheimer-s-disease
#19
William James Deardorff, George T Grossberg
Currently available therapies for the treatment of Alzheimer's disease (AD) consist of cholinesterase inhibitors (ChEIs), such as donepezil, and the N-methyl-D-aspartate receptor antagonist memantine. In December 2014, the US Food and Drug Administration approved Namzaric™, a once-daily, fixed-dose combination (FDC) of memantine extended-release (ER) and donepezil for patients with moderate-to-severe AD. The FDC capsule is bioequivalent to the coadministered individual drugs, and its bioavailability is similar when taken fasting, with food, or sprinkled onto applesauce...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27754769/treatment-of-serpiginous-choroiditis-with-chlorambucil-a-report-of-17-patients
#20
Nazanin Ebrahimiadib, Bobeck S Modjtahedi, Samaneh Davoudi, C Stephen Foster
PURPOSE: To evaluate the efficacy of chlorambucil in the treatment of serpiginous choroiditis. METHODS: Patient records from the Massachusetts Eye Research and Surgery Institution (MERSI) were reviewed from over the past 10 years. In total, 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil were identified. QuantiFERON gold was negative in all of them. Chlorambucil was started at 0.15 mg/kg and dosage was titrated up using weekly white blood cell (WBC) count to achieve a target cell number of 3...
October 18, 2016: Ocular Immunology and Inflammation
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