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Drug tolerant persister

Rashad Alkasir, Yanan Ma, Fei Liu, Jing Li, Na Lv, Yong Xue, Yongfei Hu, Baoli Zhu
Acinetobacter baumannii is a nonfermenting Gram-negative bacillus. A. baumannii resistance is a significant obstacle to clinical infection treatment. The existence of persister cells (persisters) might represent the reason for therapy failure and relapse, and such cells may be the driving force behind rising resistance rates. In this study, A. baumannii ATCC 19606 was used as a target to explore the essential features of A. baumannii persisters. Antibiotic treatment of A. baumannii cultures at 50-fold the minimum inhibitory concentration resulted in a distinct plateau of surviving drug-tolerant persisters...
June 14, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Mengxiong Wang, Mary E Law, Ronald K Castellano, Brian K Law
The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells, responsible for protein synthesis, folding, sorting, and transportation. ER stress is initiated when the unfolded or misfolded protein load exceeds the capacity of the ER to properly fold protein. Tumor microenvironmental conditions, such as nutrient deprivation, hypoxia, and oxidative stress perturb protein folding and trigger chronic ER stress. Cancer cells can tolerate mild ER stress, however, persistent and severe ER stress kills cancer cells by inducing their autophagy, apoptosis, necroptosis, or immunogenic cell death...
July 2018: Critical Reviews in Oncology/hematology
Emma D Deeks
The first-in-class β3 -adrenoceptor agonist mirabegron is indicated in the EU (Betmiga™), Japan (Betanis™) and several other countries for the management of overactive bladder (OAB) syndrome. Evidence for its use in this setting includes several large phase 3 trials. Compared with placebo, oral mirabegron for 12 weeks reduced the frequency of micturition and generally also that of incontinence, with other benefits including reduced urgency, increased void volume and improved health related quality-of-life (HR-QOL)...
June 4, 2018: Drugs
Bo Wang, Hao Yao, Xianbiao Xie, Junqiang Yin, Changye Zou, Gang Huang, Jingnan Shen
PURPOSE: This study aimed to explore whether peak serum methotrexate concentration (Cmax ) correlated with adverse events, overall survival (OS) and event-free survival (EFS) in patients with primary extremity osteosarcoma. METHODS: Patients with extremity osteosarcoma who were treated at our center between 2005 and 2015 were retrospectively studied. All the patients were Enneking stage II and had received standard perioperative chemotherapy composed of high-dose methotrexate, doxorubicin, cisplatin and ifosfamide...
May 28, 2018: Cancer Chemotherapy and Pharmacology
Kamal Niaz, Faheem Maqbool, Fazlullah Khan, Fatima Ismail Hassan, Saeideh Momtaz, Mohammad Abdollahi
Diabetes mellitus (DM) is a chronic metabolic disorder in which blood glucose level raises that can result in severe complications. However, the incidence increased mostly by obesity, pregnancy, persistent corpus luteum, and diestrus phase in humans and animals. This review has focused on addressing the possible understanding and pathogenesis of spontaneous DM in canine, feline, and few wild animals. Furthermore, pancreatic associated disorders, diabetic ketoacidosis, hormonal and drug interaction with diabetes, and herbal remedies associated with DM are elucidated...
April 2018: Veterinary World
Chetan Naik, Cody Moore, Matthew Pipeling, Jonathan D'Cunha, Kristine Ruppert, Christopher Ensor, Matthew Morrell
Background: Acute cellular rejection (ACR) is a major risk factor for chronic lung allograft dysfunction after lung transplantation. Acute cellular rejection can persist or recur despite augmentation of immunosuppression by conventional methods. There are limited therapeutic options in treating these recurrent and refractory ACRs. We describe our experience with cyclophosphamide therapy for recurrent and refractory ACR in lung transplant recipients. Methods: Six consecutive patients who were treated with cyclophosphamide for recurrent or refractory ACR were included in the series...
May 2018: Transplantation Direct
Abdullah M Khan, Jameel Muzaffar, Hermant Murthy, John R Wingard, Jan S Moreb
Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance...
2018: Case Reports in Hematology
Lori L Burrows
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen, designated by the World Health Organization as a critical priority for development of new therapeutics due to high levels of intrinsic and acquired antibiotic resistance. Other challenges include its versatility (it can persist in the environment and most strains are capable of causing disease in compromised hosts), robust efflux mechanisms that limit drug penetration, and the propensity to form antimicrobial-tolerant biofilms. Novel therapeutics in development to prevent or treat P...
May 17, 2018: ACS Infectious Diseases
Mauren K Tavares, Suellen Dos Reis, Nicolle Platt, Isabella A Heinrich, Ingrid A V Wolin, Rodrigo B Leal, Manuella P Kaster, Ana Lúcia S Rodrigues, Andiara E Freitas
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most robust neurobiological findings in the pathophysiology of major depressive disorder (MDD) over the last 40 years. The persistent increase in glucocorticoids levels induces morphological and anatomical changes in the brain, especially in the hippocampus. Ketamine represents a major advance for the treatment of MDD, however the psychotomimetic effects of this compound limit its widespread use. Agmatine is a neuromodulator that has been shown to be a putative novel and well-tolerated antidepressant/augmenter drug...
May 12, 2018: Neurochemistry International
Thomas S W Park, Andy Kuo, Maree T Smith
Globally, low back pain (LBP) is one of the most common health problems affecting humans. The lifetime prevalence of non-specific LBP is approximately 84%, with the chronic prevalence at about 23%. Chronic LBP in humans is defined as LBP that persists for more than 12 weeks without a significant pain improvement. Although there are numerous evidence-based guidelines on the management of acute LBP, this is not the case for chronic LBP, which is regarded as particularly difficult to treat. Research aimed at discovering new drug treatments for alleviation of chronic mechanical LBP is lacking due to the paucity of knowledge on the pathobiology of this condition, despite its high morbidity in the affected adult population...
May 12, 2018: Inflammopharmacology
María E Mingot-Castellano, Isabel S Caparrós, Fernando Fernández, María Del Mar Perera-Alvarez, Reyes Jimenez-Bárcenas, Alberto Casaus García, Manuel González-Silva, María Yera-Cobo, María M Nieto-Hernandez, María J Rodríguez-Fernandez, Dana Díaz-Canales
: Thrombopoietin receptor agonist (TPO-RAs) have demonstrated good efficacy and tolerance in clinical trials in refractory chronic primary immune thrombocytopenia (ITP) or chronic ITP with contraindication for splenectomy. No head-to-head study is available, and differences in trials design do not allow comparisons. Information on the use of TPO-RAs in nonchronic ITP is scant. We described our experience with TPO-RAs in ITP (chronic, persistent and newly diagnosed ITP) in routine clinical practice. Retrospective series of 100 adult ITP patients was analysed; 41 treated with eltrombopag, 37 with romiplostim and 22 with both...
June 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Junshik Hong, Soo-Mee Bang, Yeung-Chul Mun, Ho-Young Yhim, Jaehoon Lee, Hyeong-Seok Lim, Doyeun Oh
Background: In the current study, we aimed to investigate the efficacy and safety of intravenous immunoglobulin (IVIg)-SN 10%, a new 10% IVIg formulation, in adult patients with severe primary immune thrombocytopenia (ITP; platelet count < 20 × 109 /L). Methods: Patients diagnosed as primary ITP, aged 19 years old or more, and had a platelet count of < 20 × 109 /L by screening complete blood cell count performed within 2 weeks of study commencement were eligible...
May 7, 2018: Journal of Korean Medical Science
Gurupreet S Sethi, Amarjit S Naura
Persistent inflammation and remodeling of airways are the major hallmarks of asthma. Though airway inflammation diminishes in ovalbumin (OVA)-based mouse model of chronic asthma owing to immune-tolerance linked with repeated allergen exposure, which limits the application of the disease model. Accordingly, the present study was designed to develop a murine model of chronic asthma which presents persistent airway inflammation coupled with remodeling traits. Herein, OVA-sensitized BALB/c mice were challenged with increasing (modified protocol) or constant concentration (conventional protocol) of the allergen for 6 weeks; 3 times/week...
May 2, 2018: International Immunopharmacology
Tiina A Jokela, Agnete S T Engelsen, Agata Rybicka, Fanny A Pelissier Vatter, James C Garbe, Masaru Miyano, Crina Tiron, Dan Ferariu, Lars A Akslen, Martha R Stampfer, James B Lorens, Mark A LaBarge
The existence of rare cancer cells that sporadically acquire drug-tolerance through epigenetic mechanisms is proposed as one mechanism that drives cancer therapy failure. Here we provide evidence that specific microenvironments impose non-sporadic expression of proteins related to epithelial plasticity and drug resistance. Microarrays of robotically printed combinatorial microenvironments of known composition were used to make cell-based functional associations between microenvironments, which were design-inspired by normal and tumor-burdened breast tissues, and cell phenotypes...
2018: Frontiers in Cell and Developmental Biology
Armand Drieu la Rochelle, Karel Guillemyn, Maria Dumitrascuta, Charlotte Martin, Valérie Utard, Raphaëlle Quillet, Séverine Schneider, François Daubeuf, Tom Willemse, Pieter Mampuys, Bert U W Maes, Nelly Frossard, Frédéric Bihel, Mariana Spetea, Frédéric Simonin, Steven Ballet
Opioid analgesics, such as morphine, oxycodone and fentanyl, are the cornerstones for treating moderate to severe pain. However, upon chronic administration, their efficiency is limited by prominent side effects such as analgesic tolerance and dependence liability. Neuropeptide FF (NPFF) and its receptors (NPFF1R and NPFF2R) are recognized as an important pronociceptive system involved in opioid-induced hyperalgesia and analgesic tolerance. Herein, we report the design of multitarget peptidomimetic compounds that show high affinity binding to the mu opioid receptor (MOPr) and NPFFRs...
April 26, 2018: Pain
Gustavo Gonzalez-Cuevas, Remi Martin-Fardon, Tony M Kerr, David G Stouffer, Loren H Parsons, Dana C Hammell, Stan L Banks, Audra L Stinchcomb, Friedbert Weiss
Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders. Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control. Here, we evaluated the "anti-relapse" potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity...
March 22, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Alain Bruno Tagne Nouemssi
Risperidone and paliperidone palmitate are two antipsychotic drugs well tolerated in the management of schizophrenia and other psychiatric conditions. There have been few reports of tachycardia induced by either drugs. Here, we report on a 21-year-old man, with a history of schizophrenia, and who developed persistent sinus tachycardia after he was restarted on risperidone, which later worsened after administration of paliperidone palmitate for long-term management. He had no cardiovascular risk factors other than obesity, and a prior well-tolerated risperidone treatment...
April 21, 2018: BMJ Case Reports
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) treatment 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 hyperbiofilm 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...
June 2018: Antimicrobial Agents and Chemotherapy
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
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...
July 1, 2018: Physiology & Behavior
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