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Drug tolerant persister

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https://www.readbyqxmd.com/read/29661867/triclosan-is-an-aminoglycoside-adjuvant-for-the-eradication-of-pseudomonas-aeruginosa-biofilms
#1
Michael M Maiden, Alessandra M Agostinho Hunt, Mitchell P Zachos, Jacob A Gibson, Martin E Hurwitz, Martha H Mulks, Christopher M Waters
One of the most important clinical obstacles in cystic fibrosis (CF) is antibiotic treatment failure due to biofilms produced by Pseudomonas aeruginosa The ability of this pathogen to survive eradication by tobramycin and pathoadapt into a hyper-biofilm state leading to chronic infections is key to its success. Retrospective studies have demonstrated that preventing this pathoadaptation by improving eradication is essential to extend the lives of CF patients. To identify adjuvants that enhance tobramycin eradication of P...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29658950/microbial-biofilms-and-their-impact-on-medical-areas-physiopathology-diagnosis-and-treatment
#2
Silvestre Ortega-Peña, Edgar Hernández-Zamora
Biofilms are communities of microorganisms that grow aggregated and surrounded by an extracellular matrix, which they produce and favors them to adhere covalently to inert and living surfaces; it also helps them to develop high tolerance to molecules with antimicrobial activity. Moreover, biofilms are associated with chronic and persistent infections, which negatively impact different medical areas since they generate high costs to health care systems and patients every year because they are difficult to treat with conventional antimicrobial drugs...
2018: Boletín Médico del Hospital Infantil de México
https://www.readbyqxmd.com/read/29626506/hippocampal-glial-cells-modulate-morphine-induced-behavioral-responses
#3
Fatemehsadat Seyedaghamiri, Soomaayeh Heysieattalab, Narges Hosseinmardi, Mahyar Janahmadi, Azadeh Elahi-Mahani, Farhad Salari, Mehdi Golpayegani, Habibeh Khoshbouei
Drugs of abuse cause persistent alterations in synaptic plasticity that is thought to underlie addictive-like behaviors. Although, the perisynaptic glial cells are implicated in metabolic maintenance and support of the nervous systems, accumulating evidence suggests that glial cells exert a modulatory action on synaptic functions and participate in synaptic plasticity. However, it is well-documented that glial cells are associated with the acquisition of rewarding effects of abused drugs. The role of hippocampal glial cells in addictive-like behaviors remains poorly understood...
April 4, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29594972/a-pharmacological-rationale-to-reduce-the-incidence-of-opioid-induced-tolerance-and-hyperalgesia-a-review
#4
REVIEW
Giustino Varrassi, Mariella Fusco, Stephen D Skaper, Daniele Battelli, Panagiotis Zis, Stefano Coaccioli, Maria Caterina Pace, Antonella Paladini
Chronic pain is an important health and social problem. Misuse and abuse of opioids in chronic non-cancer pain management seem to be a huge problem, in some countries. This could probably affect the normal use of such analgesics in patients in need of them. Basic and clinical researches should find the solution to mitigate the potential damage. Dysregulation of mast cell and microglia activation plays an important role in the pathogenesis and management of chronic pain. Persistent mast cell activation sensitizes nociceptors and initiates central nervous system inflammatory processes, involving microglial cell activation and sensitization of spinal somatosensory neurons...
March 28, 2018: Pain and Therapy
https://www.readbyqxmd.com/read/29579828/chronic-pain-treatment-with-cannabidiol-in-kidney-transplant-patients-in-uruguay
#5
L Cuñetti, L Manzo, R Peyraube, J Arnaiz, L Curi, S Orihuela
BACKGROUND: Chronic pain is a major therapeutic problem in kidney transplant patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory drugs. Benefits in chronic pain treatment with cannabidiol (CBD) have been reported. This study assesses the effect, safety, and possible drug interactions in kidney transplant patients treated with CBD for chronic pain. METHODS: We assessed patients who asked to receive CBD for pain treatment. Doses were increased from 50 to 150 mg twice a day for 3 weeks...
March 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29563895/novel-somatostatin-receptor-ligands-therapies-for-acromegaly
#6
REVIEW
Rosa Maria Paragliola, Roberto Salvatori
Surgery is considered the treatment of choice in acromegaly, but patients with persistent disease after surgery or in whom surgery cannot be considered require medical therapy. Somatostatin receptor ligands (SRLs) octreotide (OCT), lanreotide, and the more recently approved pasireotide, characterized by a broader receptor ligand binding profile, are considered the mainstay in the medical management of acromegaly. However, in the attempt to offer a more efficacious and better tolerated medical approach, recent research has been aimed to override some limitations related to the use of currently approved drugs and novel SRLs therapies, with potential attractive features, have been proposed...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29560343/phenotypic-plasticity-bet-hedging-and-androgen-independence-in-prostate-cancer-role-of-non-genetic-heterogeneity
#7
REVIEW
Mohit Kumar Jolly, Prakash Kulkarni, Keith Weninger, John Orban, Herbert Levine
It is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we focus on alternate mechanisms-those without mutations, such as phenotypic plasticity and stochastic cell-to-cell variability that can also evade drug attacks by giving rise to drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria and has also recently garnered attention in cancer. We draw a parallel between bacterial persistence and resistance against androgen deprivation therapy in prostate cancer (PCa), the primary standard care for metastatic disease...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29559967/identification-of-genes-involved-in-bacteriostatic-antibiotic-induced-persister-formation
#8
Peng Cui, Hongxia Niu, Wanliang Shi, Shuo Zhang, Wenhong Zhang, Ying Zhang
Persister cells are metabolically quiescent multi-drug tolerant fraction of a genetically sensitive bacterial population and are thought to be responsible for relapse of many persistent infections. Persisters can be formed naturally in the stationary phase culture, and also can be induced by bacteriostatic antibiotics. However, the molecular basis of bacteriostatic antibiotic induced persister formation is unknown. Here, we established a bacteriostatic antibiotic induced persister model and screened the Escherichia coli single gene deletion mutant library for mutants with defect in rifampin or tetracycline induced persistence to ofloxacin...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29558972/dolutegravir-based-anti-retroviral-therapy-is-effective-and-safe-in-hiv-infected-paediatric-patients
#9
Eugenia Bruzzese, Andrea Lo Vecchio, Andrea Smarrazzo, Orsola Tambaro, Giulia Palmiero, Giovanni Bonadies, Alfredo Guarino
BACKGROUND: Treatment of HIV infection in adolescents is challenging due to long duration of therapy and poor adherence. Recently, the integrase strand transfer inhibitor dolutegravir (DTG) has been approved for the use in adolescents with HIV, but evidence in clinical practice is very limited. METHODS: We describe six cases of HIV-infected children/adolescents successfully treated with DTG-based regimen. Data relative to children/adolescents managed at the Referral Center for Pediatric HIV/AIDS of the University of Naples were reviewed...
March 20, 2018: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/29549468/a-multicentre-observational-analysis-of-persistence-to-treatment-in-the-new-multiple-sclerosis-era-the-respect-study
#10
Roberta Lanzillo, Luca Prosperini, Claudio Gasperini, Marcello Moccia, Roberta Fantozzi, Carla Tortorella, Viviana Nociti, Pietro Annovazzi, Paola Cavalla, Marta Radaelli, Simona Malucchi, Valentina Torri Clerici, Laura Boffa, Fabio Buttari, Paolo Ragonese, Giorgia Teresa Maniscalco, Massimiliano Di Filippo, Maria Chiara Buscarinu, Federica Pinardi, Antonio Gallo, Giancarlo Coghe, Ilaria Pesci, Alice Laroni, Alberto Gajofatto, Massimiliano Calabrese, Valentina Tomassini, Eleonora Cocco, Claudio Solaro
In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing-remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12 months...
March 16, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29540562/monoacylglycerol-lipase-inhibitors-reverse-paclitaxel-induced-nociceptive-behavior-and-proinflammatory-markers-in-a-mouse-model-of-chemotherapy-induced-neuropathy
#11
Zachary Curry, Jenny Wilkerson, Deniz Bagdas, Sarah Kyte, Nipa Patel, Giulia Donvito, Mohammed A Mustafa, Justin Poklis, Micah Niphakis, Ku-Lung Hsu, Benjamin F Cravatt, David A Gewirtz, M Imad Damaj, Aron H Lichtman
Although paclitaxel effectively treats various cancers, its debilitating peripheral neuropathic pain side effects often persist long after treatment has ended. Therefore, a compelling need exists for the identification of novel pharmacologic strategies to mitigate this condition. As inhibitors of monoacylglycerol lipase (MAGL), the primary hydrolytic enzyme of the endogenous cannabinoid 2-arachidonyolglycerol, produce antinociceptive effects in numerous rodent models of pain, we investigated whether inhibitors of this enzyme (i...
March 14, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29537449/phase-2-randomized-dose-ranging-study-of-oxymetazoline-cream-for-treatment-of-persistent-facial-erythema-associated-with-rosacea
#12
Janet DuBois, Jeffrey S Dover, Terry M Jones, Robert A Weiss, David R Berk, Gurpreet Ahluwalia
BACKGROUND: Rosacea is a chronic dermatologic condition with limited treatment options. OBJECTIVE: This phase 2 study evaluated the optimal oxymetazoline dosing regimen in patients with moderate to severe persistent facial erythema of rosacea. METHODS: Patients were randomly assigned to oxymetazoline cream, 0.5%, 1.0%, or 1.5%, or vehicle, administered once daily (QD) or twice daily (BID) for 28 consecutive days. The primary efficacy endpoint was the proportion of patients with ≥2-grade improvement from baseline on the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment of erythema (SSA-1) on day 28...
March 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29537447/pivotal-trial-of-the-efficacy-and-safety-of-oxymetazoline-cream-1-0-for-the-treatment-of-persistent-facial-erythema-associated-with-rosacea-findings-from-the-second-reveal-trial
#13
Leslie Baumann, David J Goldberg, Linda Stein Gold, Emil A Tanghetti, Edward Lain, Joely Kaufman, Emily Weng, David R Berk, Gurpreet Ahluwalia
Rosacea is a chronic dermatologic condition with limited treatment options, particularly for persistent erythema. This pivotal phase 3 study evaluated oxymetazoline, an a1A-adrenoceptor agonist, for the treatment of moderate to severe persistent erythema of rosacea. Eligible patients were randomly assigned 1:1 to receive oxymetazoline cream 1.0% or vehicle applied topically to the face once daily for 29 days. The primary efficacy outcome was ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for rosacea facial redness (SSA) (composite success) at 3, 6, 9, and 12 hours postdose on day 29...
March 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29525516/-management-of-drug-resistant-epilepsy
#14
Marine Loizon, Sylvain Rheims
Epilepsy is considered as drug-resistant when seizures persist despite the administration of 2 antiepileptic drugs adapted to the patient's needs, with an effective dosage, well-tolerated, whether as a single agent or in combination. Any patient suffering from drug-resistant focal epilepsy should be evaluated at least once in a tertiary epilepsy centre to discuss the appropriateness of a pre-surgical work-up. In drug-resistant epilepsy, the determinants of quality of life are multifactorial and not exclusively linked to the seizure frequency...
March 2018: La Presse Médicale
https://www.readbyqxmd.com/read/29521682/small-bowel-bleeding-cause-and-the-role-of-endoscopy-and-medical-therapy
#15
Stefania Chetcuti Zammit, Reena Sidhu
PURPOSE OF REVIEW: The objective is to provide an overview on the cause of small bowel bleeding. We discuss the role of small bowel endoscopy in the management of small bowel bleeding and provide an outline of pharmacotherapy that can be additionally beneficial. RECENT FINDINGS: Small bowel capsule endoscopy (SBCE) is the initial diagnostic investigation of choice in small bowel bleeding. Computed tomography (CT) can be helpful in the context of small bowel tumours...
May 2018: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/29515037/interleukin-7-restores-lymphocytes-in-septic-shock-the-iris-7-randomized-clinical-trial
#16
Bruno Francois, Robin Jeannet, Thomas Daix, Andrew H Walton, Matthew S Shotwell, Jacqueline Unsinger, Guillaume Monneret, Thomas Rimmelé, Teresa Blood, Michel Morre, Anne Gregoire, Gail A Mayo, Jane Blood, Scott K Durum, Edward R Sherwood, Richard S Hotchkiss
BACKGROUND: A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion of CD4+ and CD8+ T cells. Interleukin-7 (IL-7) is an antiapoptotic common γ-chain cytokine that is essential for lymphocyte proliferation and survival. Clinical trials of IL-7 in over 390 oncologic and lymphopenic patients showed that IL-7 was safe, invariably increased CD4+ and CD8+ lymphocyte counts, and improved immunity. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial of recombinant human IL-7 (CYT107) in patients with septic shock and severe lymphopenia...
March 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29510687/bacterial-risk-factors-for-treatment-failure-and-relapse-among-patients-with-isoniazid-resistant-tuberculosis
#17
Phan Vuong Khac Thai, Dang Thi Minh Ha, Nguyen Thi Hanh, Jeremy Day, Sarah Dunstan, Nguyen Thi Quynh Nhu, Vo Sy Kiet, Nguyen Huu Lan, Nguyen Huy Dung, Nguyen Thi Ngoc Lan, Nguyen Thuong Thuong, Nguyen Ngoc Lan, Phạm Thị Thúy Liễu, Nguyễn Thị Hồng, Đào Công Điệp, Nguyễn Thị Kim Thanh, Nguyễn Văn Hội, Nguyễn Văn Nghĩa, Trương Ngọc Đại, Hoàng Quang Minh, Nguyễn Văn Thơm, Jeremy Farrar, Maxine Caws
BACKGROUND: Drug resistant tuberculosis (TB) is increasing in prevalence worldwide. Treatment failure and relapse is known to be high for patients with isoniazid resistant TB treated with standard first line regimens. However, risk factors for unfavourable outcomes and the optimal treatment regimen for isoniazid resistant TB are unknown. This cohort study was conducted when Vietnam used the eight month first line treatment regimen and examined risk factors for failure/relapse among patients with isoniazid resistant TB...
March 6, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29503968/environmental-xenobiotic-exposure-and-autoimmunity
#18
K Michael Pollard, Joseph M Christy, David M Cauvi, Dwight H Kono
Susceptibility to autoimmune diseases is dependent on multigenic inheritance, environmental factors, and stochastic events. Although there has been substantial progress in identifying predisposing genetic variants, a significant challenge facing autoimmune disease research is the identification of the specific events that trigger loss of tolerance, autoreactivity and ultimately autoimmune disease. Accordingly, studies have indicated that a wide range of extrinsic factors including drugs, chemicals, microbes, and other environmental factors can induce autoimmunity, particularly systemic autoimmune diseases such as lupus...
August 2018: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/29487290/src-mediated-regulation-of-the-pi3k-pathway-in-advanced-papillary-and-anaplastic-thyroid-cancer
#19
Thomas C Beadnell, Kelsey W Nassar, Madison M Rose, Erin G Clark, Brian P Danysh, Marie-Claude Hofmann, Nikita Pozdeyev, Rebecca E Schweppe
Advanced stages of papillary and anaplastic thyroid cancer continue to be plagued by a dismal prognosis, which is a result of limited effective therapies for these cancers. Due to the high proportion of thyroid cancers harboring mutations in the MAPK pathway, the MAPK pathway has become a focal point for therapeutic intervention in thyroid cancer. Unfortunately, unlike melanoma, a similar responsiveness to MAPK pathway inhibition has yet to be observed in thyroid cancer patients. To address this issue, we have focused on targeting the non-receptor tyrosine kinase, Src, and we and others have demonstrated that targeting Src results in inhibition of growth, invasion, and migration both in vitro and in vivo, which can be enhanced through the combined inhibition of Src and the MAPK pathway...
February 28, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29484607/treatment-of-tardive-dyskinesia-a-general-overview-with-focus-on-the-vesicular-monoamine-transporter-2-inhibitors
#20
Nicki Niemann, Joseph Jankovic
Tardive dyskinesia (TD) encompasses the spectrum of iatrogenic hyperkinetic movement disorders following exposure to dopamine receptor-blocking agents (DRBAs). Despite the advent of atypical or second- and third-generation antipsychotics with a presumably lower risk of complications, TD remains a persistent and challenging problem. Prevention is the first step in mitigating the risk of TD, but early recognition, gradual withdrawal of offending medications, and appropriate treatment are also critical. As TD is often a persistent and troublesome disorder, specific antidyskinetic therapies are often needed for symptomatic relief...
February 26, 2018: Drugs
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