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Drugs in emergency

C Koutserimpas, G Samonis, M N Plataki, C Bikis, G Kontakis, D P Kofteridis
AIM: Few series of osteomyelitis due to multi-drug (MDR) or extensively-drug resistant (XDR) gram-negative bacteria exist. A retrospective study of MDR and XDR gram-negative osteomyelitis cases was performed, aiming to investigate causative organisms, proper surgical and medical management, as well as outcome. PATIENTS AND METHODS: All patients, treated at the University hospital of Crete between 2007 and 2016 for acute osteomyelitis, due to MDR or XDR gram-negative pathogens were evaluated...
September 2018: Il Giornale di Chirurgia
Ming You, Chuanrui Chen, Leilei Xu, Fangzhi Mou, Jianguo Guan
Micro/nanomotors (MNMs) are micro/nanoscale devices that can convert energy from their surroundings into autonomous motion. With this unique ability, they may revolutionize application fields ranging from active drug delivery to biological surgeries, environmental remediation, and micro/nanoengineering. To complete these applications, MNMs are required to have a vital capability to reach their destinations. Employing external fields to guide MNMs to the targets is common and effective way. However, in application scenarios where targets are generally unknown or dynamically change, MNMs must possess the capability of self-navigation or self-targeting...
November 16, 2018: Accounts of Chemical Research
Daniele Roberto Giacobbe, Malgorzata Mikulska, Claudio Viscoli
The emergence and diffusion of multidrug resistant Gram-negative bacteria (MDR-GNB) is an unprecedented threat, with prevalences as high as 10-50% being reported in many countries. Areas covered: In the present review we discuss the management of infections due to MDR-GNB, focusing in particular on current strategies and novel agents with already available results from phase 3 randomized controlled trials. Expert commentary: Some new drugs, such as ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam, which have become available in the past months, have increased our chance of improving survival in severe carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae infections; while others, with potent activity against carbapenem-resistant Acinetobacter baumannii which is currently the highest priority regarding the need for novel agents, will become available in the near future...
November 16, 2018: Expert Review of Clinical Pharmacology
Jean-Philip George Lumb, Matthew W Halloran
The elucidation of substrate-protein interactions is an important component of the drug development process. Due to the complexity of native cellular environments, elucidating these fundamental biochemical interactions remains challenging. Photoaffinity labeling (PAL) is a versatile technique that can provide insight into ligand-target interactions. By judicious modification of substrates with a photoreactive group, PAL creates a covalent crosslink between a substrate and its biolgical target following UV-irradiation...
November 15, 2018: Chemistry: a European Journal
Christopher M DeGiorgio, Ashley Curtis, Dieter Hertling, Brian D Moseley
Sudden unexpected death in epilepsy (SUDEP) is one of the most important direct epilepsy-related causes of death, with an incidence in adults of 1.2 per 1000 person years. Generalized tonic-clonic seizures have consistently emerged as the leading risk factor for SUDEP, particularly when such seizures are uncontrolled. High seizure burden, lack of antiepileptic drug (AED) treatment, polytherapy, intellectual disability, and prone position at the time of death are other key risk factors. Unfortunately, despite advances in treatment, overall mortality rates in epilepsy are rising...
November 15, 2018: Acta Neurologica Scandinavica
Rahul Mittal, Frank W Woo, Carlo S Castro, Madeline A Cohen, Joana Karanxha, Jeenu Mittal, Tanya Chhibber, Vasanti M Jhaveri
Before a lead compound goes through a clinical trial, preclinical studies utilize two-dimensional (2D) in vitro models and animal models to study the pharmacodynamics and pharmacokinetics of that lead compound. However, these current preclinical studies may not accurately represent the efficacy and safety of a lead compound in humans, as there has been a high failure rate of drugs that enter clinical trials. All of these failures and the associated costs demonstrate a need for more representative models of human organ systems for screening in the preclinical phase of drug development...
November 15, 2018: Journal of Cellular Physiology
Asad Ali, Abdul Wahab Arif, Chandur Bhan, Deepak Kumar, Muhammad Bilal Malik, Zohaib Sayyed, Khawaja Hassan Akhtar, Malik Qistas Ahmad
A majority of the elderly suffer from chronic pain that significantly alters their daily activities and imposes an enormous burden on health care. Multiple comorbidities and the risk of polypharmacy in the elderly make it a challenge to determine the appropriate drug, dosage, and maintenance of therapy. Opioids are the most commonly used agents for this purpose in the elderly. The aim of this article is to discuss both the current well-established therapies used for managing chronic pain in the elderly and also the emerging newer therapies...
September 13, 2018: Curēus
Laurent Dortet, Anais Potron, Rémy A Bonnin, Patrick Plesiat, Thierry Naas, Alain Filloux, Gerald Larrouy-Maumus
With the dissemination of extremely drug resistant bacteria, colistin is now considered as the last-resort therapy for the treatment of infection caused by Gram-negative bacilli (including carbapenemase producers). Unfortunately, the increase use of colistin has resulted in the emergence of resistance as well. In A. baumannii, colistin resistance is mostly caused by the addition of phosphoethanolamine to the lipid A through the action of a phosphoethanolamine transferase chromosomally-encoded by the pmrC gene, which is regulated by the two-component system PmrA/PmrB...
November 15, 2018: Scientific Reports
Zilin Li, Shen Kiat Lim, Xu Liang, Yoon Pin Lim
The transcriptional coactivator WW domain-binding protein 2 (WBP2) is an emerging oncogene and serves as a node between the signaling protein Wnt and other signaling molecules and pathways, including epidermal growth factor receptor, estrogen receptor/progesterone receptor, and the Hippo pathway. The upstream regulation of WBP2 is well-studied, but its downstream activity remains unclear. Here, we elucidated WBP2's role in triple-negative breast cancer (TNBC), in which Wnt signaling is predominantly activated...
November 15, 2018: Journal of Biological Chemistry
Funda Meric-Bernstam, Amber Johnson, Ecaterina E Ileana Dumbrava, Kanwal Raghav, Kavitha Balaji, Michelle Bhatt, Rashmi K Murthy, Jordi Rodon, Sarina A Piha-Paul
The introduction of HER2-targeted therapy for breast and gastric patients with ERBB2(HER2) amplification/overexpression has led to dramatic improvements in oncologic outcomes. In the past 20 years, five HER2-targeted therapies have been FDA approved, four in the past 8 years. HER2-targeted therapy similarly was found to improve outcomes in HER2-positive gastric cancer. Over the past decade, with the introduction of next generation sequencing into clinical practice, our understanding of HER2 biology has dramatically improved...
November 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Suzanne Trudel, Nikoletta Lendvai, Rakesh Popat, Peter M Voorhees, Brandi Reeves, Edward N Libby, Paul G Richardson, Larry D Anderson, Heather J Sutherland, Kwee Yong, Axel Hoos, Michele M Gorczyca, Soumi Lahiri, Zangdong He, Daren J Austin, Joanna B Opalinska, Adam D Cohen
BACKGROUND: B-cell maturation antigen (BCMA) is a cell-surface receptor of the tumour necrosis superfamily required for plasma cell survival. BMCA is universally detected on patient-derived myeloma cells and has emerged as a selective antigen to be targeted by novel treatments in multiple myeloma. We assessed the safety, tolerability, and preliminary clinical activity of GSK2857916, a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin F, in patients with relapsed and refractory multiple myeloma...
November 12, 2018: Lancet Oncology
Daniel R Willett, Jason D Rodriguez
We present a rapid Raman assay for on-site analysis of stockpiled drugs in aqueous solution. This approach was tested on Tamiflu (oseltamivir phosphate). Tamiflu is a drug approved by the FDA for treatment of influenza and is the most common antiviral included in stockpiles for use in the event of a national emergency. Rapid assays were performed on three concentrations (30, 45, and 75 mg) of oseltamivir using three different portable & handheld Raman instruments. PLS regression models were developed to establish a calibration curve and applied to the Tamiflu samples...
December 31, 2018: Analytica Chimica Acta
T Hamp, J Baron-Stefaniak, M Krammel, B Reiter, A Langauer, T Stimpfl, W Plöchl
BACKGROUND: Ketamine is routinely used in operating theatres, emergency departments, ICUs, and even outpatient units. Despite the widespread use of ketamine, only basic aspects of its interactions with inhalation anaesthetic agents are known, and formal testing of interactions in humans is lacking. The minimum alveolar concentration (MAC) of inhalation anaesthetics is used to guide the depth of anaesthesia, and several drugs are known to influence the MAC. The aim of this study was to investigate whether intravenous application of ketamine influences the MAC of sevoflurane in humans...
December 2018: British Journal of Anaesthesia
Philippe J Domeyer, Vasiliki Katsari, Pavlos Sarafis, Vassilis Aletras, Dimitris Niakas
BACKGROUND: The penetration of generic medicines in the pharmaceutical market is influenced, among others, by the consumer's attitude upon them. The attitude of students in health management and recent alumni is particularly important, as they constitute tomorrow's policymakers. The aim of our study was to assess their attitude, perception and knowledge towards generic medicines. METHODS: A cross-sectional study was undertaken, involving students in Health Management and recent alumni...
November 15, 2018: BMC Medical Education
Evgenia Dueva, Kriti Singh, Anastasia Kalyta, Eric LeBlanc, Paul S Rennie, Artem Cherkasov
Orphan nuclear receptor TLX (NR2E1) plays a critical role in the regulation of neural stem cells (NSC) as well as in the development of NSC-derived brain tumors. In the last years, new data have emerged implicating TLX in prostate and breast cancer. Therefore, inhibitors of TLX transcriptional activity may have a significant impact on the treatment of several critical malignancies. However, the TLX protein possesses a non-canonical ligand-binding domain (LBD), which lacks a ligand-binding pocket (conventionally targeted in case of nuclear receptors) that complicates the development of small molecule inhibitors of TLX...
November 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Marco Vidotto, Daniele Dini, Elena De Momi
Patients affected by glioblastomas have a very low survival rate. Emerging techniques, such as convection enhanced delivery (CED), need complex numerical models to be effective; furthermore, the estimation of the main parameters to be used to instruct constitutive laws in simulations represents a major challenge. This work proposes a new method to compute tortuosity, a key parameter for drug diffusion in fibrous tissue, starting from a model which incorporates the main white matter geometrical features. It is shown that tortuosity increases from 1...
July 2018: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Kai-Yuan Chen, Tara Srinivasan, Christopher Lin, Kuei-Ling Tung, Ziyang Gao, David S Hsu, Steven M Lipkin, Xiling Shen
Organoids are three-dimensional cell cultures that mimic organ functions and structures. The organoid model has been developed as a versatile in vitro platform for stem cell biology and diseases modeling. Tumor organoids are shown to share ~ 90% of genetic mutations with biopsies from same patients. However, it's not clear whether tumor organoids recapitulate the cellular heterogeneity observed in patient tumors. Here, we used single-cell RNA-Seq to investigate the transcriptomics of tumor organoids derived from human colorectal tumors, and applied machine learning methods to unbiasedly cluster subtypes in tumor organoids...
July 2018: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Suowen Xu, Danielle Kamato, Peter J Little, Shinichi Nakagawa, Jaroslav Pelisek, Zheng Gen Jin
Atherosclerosis, the principal cause of cardiovascular death worldwide, is a pathological disease characterized by fibro-proliferation, chronic inflammation, lipid accumulation, and immune disorder in the vessel wall. As the atheromatous plaques develop into advanced stage, the vulnerable plaques are prone to rupture, which causes acute cardiovascular events, including ischemic stroke and myocardial infarction. Emerging evidence has suggested that atherosclerosis is also an epigenetic disease with the interplay of multiple epigenetic mechanisms...
November 12, 2018: Pharmacology & Therapeutics
Amanda St Ivany, Susan Kools, Phyllis Sharps, Linda Bullock
AIM: The aim of this study was to understand the social context of the lives of women who experienced a head injury from intimate partner violence. BACKGROUND: Sixty percent to 92% of survivors of intimate partner violence receive head trauma during the abuse. Little research exists regarding the episodes of abuse when women receive a head injury, or the reasons women might not seek medical care for the head injury or the abuse. METHOD: Twenty-one interviews from nine women who self-reported passing out from being hit in the head were analyzed using thematic analysis...
October 2018: Journal of Forensic Nursing
Irina A Leneva, Irina N Falynskova, Nailya R Makhmudova, Artem A Poromov, Svetlana B Yatsyshina, Viktor V Maleev
Antiviral drugs can play a significant role in the control of influenza. Umifenovir (Arbidol) is licensed and widely used in Russia for the prophylaxis and/or treatment of influenza. We evaluated the susceptibility to umifenovir of reference influenza A and B viruses and influenza A viruses isolated from patients in the ARBITR clinical trial in 2012-2014 seasons. Using an MDCK cell-based ELISA, we showed that the replication of antigenically dominant human influenza A and B viruses was efficiently inhibited by umifenovir...
November 15, 2018: Journal of Medical Virology
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