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Drug tolerant persister

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https://www.readbyqxmd.com/read/28238966/managing-lafora-body-disease-with-vagal-nerve-stimulation
#1
Mohamad A Mikati, Faysal Tabbara
A 17-year-old female, of consanguineous parents, presented with a history of seizures and cognitive decline since the age of 12 years. She had absence, focal dyscognitive, generalized myoclonic, and generalized tonic-clonic seizures, all of which were drug resistant. The diagnosis of Lafora body disease was made based on a compatible clinical, EEG, seizure semiology picture and a disease-causing homozygous mutation in the EPM2A gene. A vagus nerve stimulator (VNS) was inserted and well tolerated with a steady decrease and then stabilization in seizure frequency during the six months following insertion (months 1-6)...
February 22, 2017: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/28221264/efficacy-and-safety-of-combined-oral-chelation-with-deferiprone-and-deferasirox-in-children-with-%C3%AE-thalassemia-major-an-experience-from-north-india
#2
Nupur Parakh, Jagdish Chandra, Sunita Sharma, Bhavna Dhingra, Rajesh Jain, DeoNath Mahto
OBJECTIVE: A combination of desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with β-thalassemia major who do not achieve negative iron balance with monotherapy has been studied widely. However, poor compliance resulting from the need for parentral administration of desferrioxamine and its cost necessicitates combining 2 oral chelators. METHODS: A prospective study was conducted in patients with transfusion-dependent β-thalassemia major in a tertiary care center over 2 years...
February 17, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28220940/pharmacologic-conversion-during-dofetilide-treatment-for-persistent-atrial-fibrillation
#3
Jonathan S Steinberg, Yash Shah, Barbara Szepietowska
BACKGROUND: Dofetilide is a pure IKr blocker and is one of the few drugs specifically studied and approved in the United States for the management of persistent AF. Dofetilide has been noted to have a high rate of pharmacologic conversion during initial dosing in prior smaller studies. The intent of the study was to examine the safety of an inpatient loading strategy, and the incidence and patterns of pharmacologic conversion by dofetilide during the treatment of persistent AF in a large consecutive cohort...
February 21, 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#4
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28203228/encapsulation-of-antifungals-in-micelles-protects-candida-albicans-during-gall-bladder-infection
#5
Shih-Hung Hsieh, Sascha Brunke, Matthias Brock
Candida albicans is a dimorphic fungus that colonizes human mucosal surfaces with the potential to cause life-threatening invasive candidiasis. Studies on systemic candidiasis in a murine infection model using in vivo real-time bioluminescence imaging revealed persistence of C. albicans in the gall bladder under antifungal therapy. Preliminary analyses showed that bile conferred resistance against a wide variety of antifungals enabling survival in this cryptic host niche. Here, bile and its components were studied for their ability to reduce antifungal efficacy in order to elucidate the underlying mechanism of protection...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28174313/atp-dependent-persister-formation-in-escherichia-coli
#6
Yue Shan, Autumn Brown Gandt, Sarah E Rowe, Julia P Deisinger, Brian P Conlon, Kim Lewis
: Persisters are dormant variants that form a subpopulation of cells tolerant to antibiotics. Persisters are largely responsible for the recalcitrance of chronic infections to therapy. In Escherichia coli, one widely accepted model of persister formation holds that stochastic accumulation of ppGpp causes activation of the Lon protease that degrades antitoxins; active toxins then inhibit translation, resulting in dormant, drug-tolerant persisters. We found that various stresses induce toxin-antitoxin (TA) expression but that induction of TAs does not necessarily increase persisters...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28148629/monitoring-long-term-efficacy-of-fampridine-in-gait-impaired-patients-with-multiple-sclerosis
#7
Linard Filli, Björn Zörner, Sandra Kapitza, Katja Reuter, Lilla Lörincz, David Weller, Tabea Sutter, Tim Killeen, Philipp Gruber, Jens A Petersen, Michael Weller, Michael Linnebank
OBJECTIVE: To expand upon the limited knowledge of the long-term effects of prolonged-release (PR) fampridine in patients with multiple sclerosis (PwMS) regarding safety, walking improvements, and changes in drug responsiveness. METHODS: Fifty-three PwMS who completed the FAMPKIN core study were included in this extension trial. Drug efficacy was assessed in an open-label and randomized double-blind, placebo-controlled study design with regular baseline assessments over a period of 2 years using the Timed 25-Foot Walk (T25FW), 6-Minute Walk Test (6MWT), and 12-item MS Walking Scale (MSWS-12) as outcome measures...
February 1, 2017: Neurology
https://www.readbyqxmd.com/read/28148280/optimizing-adalimumab-treatment-in-psoriasis-with-concomitant-methotrexate-optimap-study-protocol-for-a-pragmatic-single-blinded-investigator-initiated-randomized-controlled-trial
#8
Celine Busard, Stef Menting, Sun-Jine van Bezooijen, Juul van den Reek, Barbara Hutten, Errol Prens, Elke de Jong, Martijn van Doorn, Phyllis Spuls
BACKGROUND: The introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases...
February 2, 2017: Trials
https://www.readbyqxmd.com/read/28145464/tdtest-easy-detection-of-bacterial-tolerance-and-persistence-in-clinical-isolates-by-a-modified-disk-diffusion-assay
#9
Orit Gefen, Betty Chekol, Jacob Strahilevitz, Nathalie Q Balaban
Antibiotic tolerance - the ability for prolonged survival under bactericidal treatments - is a potentially clinically significant phenomenon that is commonly overlooked in the clinical microbiology laboratory. Recent in vitro experiments show that high tolerance can evolve under intermittent antibiotic treatments in as little as eight exposures to high doses of antibiotics, suggesting that tolerance may evolve also in patients. However, tests for antibiotic susceptibilities, such as the disk-diffusion assay, evaluate only the concentration at which a bacterial strain stops growing, namely resistance level...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28133957/efficacy-and-safety-of-vaccination-in-pediatric-patients-with-systemic-inflammatory-rheumatic-diseases-a-systematic-review-of-the-literature
#10
Sandra Sousa, Ana Catarina Duarte, Inês Cordeiro, Joana Ferreira, Maria João Gonçalves, Tiago Meirinhos, Teresa Martins Rocha, Vasco C Romão, Maria José Santos
INTRODUCTION: Children and adolescents with systemic rheumatic diseases have an increased risk of infections. Although some infections are vaccine-preventable, immunization among patients with juvenile rheumatic diseases is suboptimal, partly due to some doubts that still persist regarding its efficacy and safety in this patient population. OBJECTIVES: To review the available evidence regarding the immunological response and the safety of vaccination in children and adolescents with systemic inflammatory rheumatic diseases (SIRD)...
November 9, 2016: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28115345/sub-inhibitory-concentrations-of-bacteriostatic-antibiotics-induce-rela-dependent-and-rela-independent-tolerance-to-%C3%AE-lactams
#11
Pavel Kudrin, Vallo Varik, Sofia Raquel Alves Oliveira, Jelena Beljantseva, Teresa Del Peso Santos, Ievgen Dzhygyr, Dominik Rejman, Felipe Cava, Tanel Tenson, Vasili Hauryliuk
The nucleotide (p)ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance and virulence. During amino acid starvation, the Escherichia coli (p)ppGpp synthetase RelA is activated by deacylated tRNA in the ribosomal A-site. An increase in (p)ppGpp is believed to drive the formation of antibiotic-tolerant persister cells, prompting the development of strategies to inhibit (p)ppGpp synthesis. We show that in a biochemical system from purified E. coli components, the antibiotic thiostrepton efficiently inhibits RelA activation by the A-site tRNA...
January 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28112516/pharmacokinetic-analysis-and-in-vivo-antitumor-efficacy-of-taccalonolides-af-and-aj
#12
April L Risinger, Jing Li, Lin Du, Raymond Benavides, Andrew J Robles, Robert H Cichewicz, John G Kuhn, Susan L Mooberry
The taccalonolides are microtubule stabilizers that covalently bind tubulin and circumvent clinically relevant forms of resistance to other drugs of this class. Efforts are under way to identify a taccalonolide with optimal properties for clinical development. The structurally similar taccalonolides AF and AJ have comparable microtubule-stabilizing activities in vitro, but taccalonolide AF has excellent in vivo antitumor efficacy when administered systemically, while taccalonolide AJ does not elicit this activity even at maximum tolerated dose...
February 24, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28110918/nitroxoline-a-broad-spectrum-biofilm-eradicating-agent-against-pathogenic-bacteria
#13
Yasmeen Abouelhassan, Qingping Yang, Hussain Yousaf, Minh Thu Nguyen, Melanie Rolfe, Gregory S Schultz, Robert W Huigens
Bacterial biofilms are surface-attached communities of slow-growing or non-replicating bacteria tolerant to conventional antibiotic therapies. Although biofilms are known to occur in ca. 80% of all bacterial infections, no therapeutic agent has been developed to eradicate bacteria housed within biofilms. We have discovered that nitroxoline, an antibacterial agent used to treat urinary tract infections, displays broad-spectrum biofilm-eradicating activities against major human pathogens, including drug-resistant Staphylococcus aureus and Acinetobacter baumannii strains...
December 6, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28100001/transplantation-tolerance-don-t-forget-about-the-b-cells
#14
REVIEW
Anita S Chong, Stella H Khiew
Establishing a state of transplantation tolerance that leads to indefinite graft survival without the need for lifelong immunosuppression has been successfully achieved in limited numbers of transplant recipients in the clinic. These successes led to studies aimed at identifying potential biomarkers that diagnose allograft tolerance and identify the patients most amenable to drug minimization, and implicated an enriched B cell signature of tolerance. The emergence of a specialized subset of regulatory B cell (Bregs) that possess immune-modulatory function in inflammation and autoimmune disease, raised the possibility that Bregs play critical roles in the promotion of transplantation tolerance and that Bregs are the underlying explanation for the B cell signature of tolerance...
January 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28095558/clinical-evaluation-of-a-4-hydroquinone-1-retinol-treatment-regimen-for-improving-melasma-and-photodamage-in-fitzpatrick-skin-types-iii-vi
#15
Marta I Rendon, Sylvia Barkovic
The bene ts of monotherapy with hydroquinone for melasma and retinoids for photodamaged skin is well established. Here we report results of a hydroquinone skincare regimen designed for melasma treatment combined with a cosmetic retinol cream on subjects presenting with both melasma and facial photodamage in a 24-week study. Improvement in melasma and photodamage ef cacy pa- rameters of melasma pigmentation intensity and melasma area and severity index (MASI), as well as overall photodamage and mottled hyperpigmentation were found by week 4, the rst post-baseline time point...
November 1, 2016: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28093662/a-cost-effectiveness-analysis-of-lisdexamfetamine-dimesylate-in-the-treatment-of-adults-with-attention-deficit-hyperactivity-disorder-in-the-uk
#16
Evelina A Zimovetz, Alain Joseph, Rajeev Ayyagari, Josephine A Mauskopf
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder in children that may persist into adulthood. Lisdexamfetamine dimesylate (LDX) is approved in many countries for ADHD treatment in children, adolescents, and adults. OBJECTIVES: Estimate the cost-effectiveness of LDX as a first- or second-line treatment for adults with ADHD from the United Kingdom (UK) National Health Service (NHS) perspective compared with methylphenidate extended release (MPH-ER) and atomoxetine (ATX)...
January 16, 2017: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
https://www.readbyqxmd.com/read/28093504/a-model-of-type-2-diabetes-in-the-guinea-pig-using-sequential-diet-induced-glucose-intolerance-and-streptozotocin-treatment
#17
Brendan K Podell, David F Ackart, Michael A Richardson, James E DiLisio, Bruce Pulford, Randall J Basaraba
Type 2 diabetes is a leading cause of morbidity and mortality among non-communicable diseases and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs in which diet-induced glucose intolerance precedes β cell cytotoxicity, two processes that are critical to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after eight weeks of feeding a high fat, high carbohydrate diet, as determined by oral glucose challenge...
January 12, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28091770/relevance-of-surgery-in-patients-with-non-variceal-upper-gastrointestinal-bleeding
#18
S Dango, T Beißbarth, E Weiss, A Seif Amir Hosseini, D Raddatz, V Ellenrieder, J Lotz, B M Ghadimi, A Beham
INTRODUCTION: Upper GI bleeding remains one of the most common emergencies with a substantial overall mortality rate of up to 30%. In severe ill patients, death does not occur due to failure of hemostasis, either medical or surgical, but mainly from comorbidities, treatment complications, and decreased tolerated blood loss. Management strategies have changed dramatically over the last two decades and include primarily endoscopic intervention in combination with acid-suppressive therapy and decrease in surgical intervention...
January 14, 2017: Langenbeck's Archives of Surgery
https://www.readbyqxmd.com/read/28079339/survey-of-bullous-pemphigoid-in-an-italian-university-hospital-clinical-epidemiological-characteristics-and-follow-up
#19
Riccardo Balestri, Giulia Odorici, Annalisa Patrizi, Salvatore D Infusino, Michela Magnano, Federico Bardazzi
BACKGROUND: The clinical-epidemiological characteristics and course of bullous pemphigoid in the general population is not clear. Few studies have been performed to date, and only one in the Italian population more than ten years ago. We decided to evaluate the characteristics and outcome of patients admitted for a bullous pemphigoid at our Hospital in the last 4 years. METHODS: We retrospectively review the last 4 years' medical records of the Department of Dermatology of the University of Bologna, identifying all patients with histological and immunological data typical for bullous pemphigoid...
January 12, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28074543/low-distress-tolerance-predicts-heightened-drug-seeking-and-taking-after-extended-abstinence-from-cocaine-self-administration
#20
Travis M Moschak, Douglas R Terry, Stacey B Daughters, Regina M Carelli
Distress tolerance (DT), defined as the ability to persist in goal-directed behavior while experiencing psychological distress, is associated with greater frequency of substance use and poor treatment outcomes. To examine a potential causal role substance use may play in DT, we developed a rodent model of DT in which rats had to press a lever within a continuously decreasing time window for reward while receiving negative feedback on failure trials. DT was defined as the time rats continued to seek reward before quitting the task...
January 11, 2017: Addiction Biology
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