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Drugs in emergency

Daniel Nichol, Mark Robertson-Tessi, Peter Jeavons, Alexander R A Anderson
Non-genetic variation in phenotypes, or bet-hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet-hedging emerges in the genotype-phenotype mapping through a simple interaction model: a molecular switch. We use simple Chemical Reaction Networks to implement stochastic switches that map gene products to phenotypes and investigate the impact of structurally distinct mappings on the evolution of phenotypic heterogeneity. Bet-hedging naturally emerges within this model and is robust to evolutionary loss through mutations to both the expression of individual genes and to the network itself...
October 21, 2016: Genetics
Jennifer C Cook, Richard H Tran, J Herbert Patterson, Jo E Rodgers
PURPOSE: The pharmacology, clinical efficacy, and safety profiles of evolving therapies for the management of chronic heart failure (HF) and acute decompensated heart failure (ADHF) are described. SUMMARY: HF confers a significant financial burden despite the widespread use of traditional guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone receptor antagonists, and the rates of HF-related mortality and hospitalization have remained unacceptably high...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
Danielle L Brunjes, Adam Castano, Autumn Clemons, Jonah Rubin, Mathew S Maurer
Wild type transthyretin cardiac amyloidosis (ATTRwt), formerly called senile cardiac amyloidosis (SCA), is almost exclusively a disorder of older adults. As the population ages, the diagnosis of ATTRwt will increase making it the most common form of cardiac amyloidosis. An important precondition to reduce under-diagnosis and misdiagnosis is to maintain a high index of suspicion for cardiac amyloidosis. Several clues can be gleaned from the clinical history, physical exam, electrocardiogram and non-invasive imaging techniques...
October 18, 2016: Journal of Cardiac Failure
Kristy Bultema, Sara Fowler, Melissa Drum, Al Reader, John Nusstein, Mike Beck
INTRODUCTION: In the treatment of patients with symptomatic irreversible pulpitis, endodontic debridement is a predictable method to relieve pain. However, there are clinical situations in which emergency care cannot be provided immediately. An unexplored treatment option in these cases may be the use of a long-acting anesthetic to reduce pain in untreated irreversible pulpitis. Some medical studies have shown potential for infiltrations of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, San Diego, CA) to prolong pain relief and reduce opioid use postoperatively...
October 18, 2016: Journal of Endodontics
Sanjib K Shrestha, Liliia M Kril, Keith D Green, Stefan Kwiatkowski, Vitaliy M Sviripa, Justin R Nickell, Linda P Dwoskin, David S Watt, Sylvie Garneau-Tsodikova
The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicrobial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity...
October 10, 2016: Bioorganic & Medicinal Chemistry
Richard J Hamilton, Vadim Keyfes, Sahil S Banka
BACKGROUND: Synthetic cannabinoids (SC) are recreational designer drugs intended to mimic delta-9-tetrahydrocannabinol while surreptitiously circumventing classification by the Drug Enforcement Administration. CASE REPORT: A 50-year-old black male arrived in the Emergency Department transported by Emergency Medical Services (EMS) for altered mental status after complaining of chest pain associated with smoking SCs. EMS found the patient with an empty foil pack labeled "Scooby Snax Limited Edition Blueberry Potpourri...
October 19, 2016: Journal of Emergency Medicine
Hui Dong, Hao Sun, Jianping Zheng
With the development of large-scale biologic databases, precision medicine is becoming a frontier in biomedical research. As a main focus of precision medicine study, cancer has been widely accepted as a disease born out of inherited genetic variations or accumulating genomic damage. At the single-cell level, microfluidics or lab-on-a-chip technology for cancer study is an emerging tool for improving risk assessment, diagnostic categories and therapeutic strategies. This work presents a multi-layer microchip for single-cell gene expression profiling...
December 1, 2016: Talanta
Bilal Demir, Tulay Yilmaz, Emine Guler, Z Pinar Gumus, Huseyin Akbulut, Ebru Aldemir, Hakan Coskunol, Demet Goen Colak, Ioan Cianga, Shuhei Yamada, Suna Timur, Takeshi Endo, Yusuf Yagci
Affinity-type sensors have emerged as outstanding platforms in the detection of diagnostic protein markers, nucleic acids and drugs. Thus, these novel platforms containing antibodies could be integrated into the monitoring systems for abused drugs. Herein, we established a novel detection platform for the analysis of a common illicit drug; methamphetamine (METH). Initially, a fluorescent-labeled polypeptide (EDOT-BTDA-Pala), derived from L-alanine N-carboxyanhydride (L-Ala-NCA) via ring-opening polymerization using 4,7-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)benzo[c][1,2,5]thiadiazole-5,6-diamine (EDOT-NH2-BTDA) as initiator, was employed as a glassy carbon electrode (GCE) covering host, in order to immobilize the METH-selective antibody...
December 1, 2016: Talanta
Suwanna Chaorattanakawee, Chanthap Lon, Krisada Jongsakul, Jariyanart Gawee, Somethy Sok, Siratchana Sundrakes, Nareth Kong, Chatchadaporn Thamnurak, Soklyda Chann, Sorayut Chattrakarn, Chantida Praditpol, Nillawan Buathong, Nichapat Uthaimongkol, Philip Smith, Narongrid Sirisopana, Rekol Huy, Satharath Prom, Mark M Fukuda, Delia Bethell, Douglas S Walsh, Charlotte Lanteri, David Saunders
BACKGROUND: The recent dramatic decline in dihydroartemisinin-piperaquine (DHA-PPQ) efficacy in northwestern Cambodia has raised concerns about the rapid spread of piperaquine resistance just as DHA-PPQ is being introduced as first-line therapy in neighbouring countries. METHODS: Ex vivo parasite susceptibilities were tracked to determine the rate of progression of DHA, PPQ and mefloquine (MQ) resistance from sentinel sites on the Thai-Cambodian and Thai-Myanmar borders from 2010 to 2015...
October 21, 2016: Malaria Journal
Alfred Amambua-Ngwa, Bakary Danso, Archibald Worwui, Sukai Ceesay, Nwakanma Davies, David Jeffries, Umberto D'Alessandro, David Conway
BACKGROUND: Previous genome-wide analyses of single nucleotide variation in Plasmodium falciparum identified evidence of an extended haplotype region on chromosome 6 in West Africa, suggesting recent positive selection. Such a pattern is not seen in samples from East Africa or South East Asia, so it could be marking a selective process specific to West Africa. Analyses of the haplotype structure in samples taken at different times could give clues to possible causes of selection. METHODS: This study investigates chromosome 6 extended haplotypes in The Gambia by analysing alleles at multiple microsatellite loci using genome sequence data previously obtained from clinical isolates collected in 2008, followed by genotyping of 13 loci in 439 isolates from 1984, 1991, 2008 and 2014...
October 21, 2016: Malaria Journal
Mair Underwood
BACKGROUND: As a result of the mainstreaming of bodybuilding, the majority of image and performance enhancing drug (IPED) users are now not athletes or competitive bodybuilders, but recreational bodybuilders. Previous approaches provide little insight into how the shift from competitive to recreational contexts impacts the use of IPEDs. METHODS: In this study an online ethnographic approach is used to explore the social lives of IPEDs in a recreational context. The study focusses on the Zyzz fandom, an international online community of thousands of recreational bodybuilders who idolise the alleged IPED user Zyzz...
October 18, 2016: International Journal on Drug Policy
Brett Wolfson-Stofko, Alex S Bennett, Luther Elliott, Ric Curtis
BACKGROUND: Though public bathroom drug injection has been documented from the perspective of people who inject drugs, no research has explored the experiences of the business managers who oversee their business bathrooms and respond to drug use. These managers, by default, are first-responders in the event of a drug overdose and thus of intrinsic interest during the current epidemic of opioid-related overdoses in the United States. This exploratory study assists in elucidating the experiences that New York City business managers have with people who inject drugs, their paraphernalia, and their overdoses...
October 18, 2016: International Journal on Drug Policy
Ismael Apud, Oriol Romaní
Ayahuasca is a psychoactive beverage from the Amazon, traditionally used by indigenous and mestizo populations in the region. Widespread international use of the beverage began in the 1990s in both secular contexts and religious/spiritual networks. This article offers an analysis of these networks as health care systems in general and for the case of Spain and specifically Catalonia, describing the emergence and characteristics of their groups, and the therapeutic itineraries of some participants. The medical anthropology perspective we take enables us to reflect on the relationship between medicine and religion, and problematize the tensions between medicalization and medical pluralism...
October 18, 2016: International Journal on Drug Policy
Kristina R Kesely, Antonella Pantaleo, Francesco M Turrini, Peter Olupot-Olupot, Philip S Low
With half of the world's population at risk for malaria infection and with drug resistance on the rise, the search for mutation-resistant therapies has intensified. We report here a therapy for Plasmodium falciparum malaria that acts by inhibiting the phosphorylation of erythrocyte membrane band 3 by an erythrocyte tyrosine kinase. Because tyrosine phosphorylation of band 3 causes a destabilization of the erythrocyte membrane required for parasite egress, inhibition of the erythrocyte tyrosine kinase leads to parasite entrapment and termination of the infection...
2016: PloS One
Thidarat Wongpinyochit, Blair F Johnston, F Philipp Seib
Silk is a promising biopolymer for biomedical and pharmaceutical applications due to its outstanding mechanical properties, biocompatibility and biodegradability, as well its ability to protect and subsequently release its payload in response to a trigger. While silk can be formulated into various material formats, silk nanoparticles are emerging as promising drug delivery systems. Therefore, this article covers the procedures for reverse engineering silk cocoons to yield a regenerated silk solution that can be used to generate stable silk nanoparticles...
October 8, 2016: Journal of Visualized Experiments: JoVE
Katie M Parkins, Amanda M Hamilton, Ashley V Makela, Yuanxin Chen, Paula J Foster, John A Ronald
Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i...
October 21, 2016: Scientific Reports
I Bravo-Osuna, V Andrés-Guerrero, P Pastoriza Abal, I T Molina-Martínez, R Herrero-Vanrell
Efficient treatment of ocular diseases can be achieved thanks to the proper use of ophthalmic formulations based on emerging pharmaceutical approaches. Among them, microtechnology and nanotechnology strategies are of great interest in the development of novel drug delivery systems to be used for ocular therapy. The location of the target site in the eye as well as the ophthalmic disease will determine the route of administration (topical, intraocular, periocular, and suprachoroidal administration) and the most adequate device...
October 20, 2016: Drug Delivery and Translational Research
Matt Shirley, Lesley J Scott
Isavuconazole is a second-generation triazole with activity against a broad spectrum of clinically important fungi. Its water-soluble prodrug, isavuconazonium sulfate (Cresemba(®)), available in interchangeable intravenous and oral formulations, is approved in the USA and EU for the treatment of adults with invasive aspergillosis and mucormycosis. In international phase III clinical trials, isavuconazole was efficacious and generally well tolerated in the treatment of these life-threatening diseases. In the phase III SECURE trial, isavuconazole was non-inferior to voriconazole for the primary treatment of invasive mould disease (primarily aspergillosis) and was associated with fewer drug-related treatment-emergent adverse events (TEAEs) than voriconazole...
October 20, 2016: Drugs
U M Stamer, U Gundert-Remy, E Biermann, J Erlenwein, W Meiβner, S Wirz, T Stammschulte
BACKGROUND: Dipyrone (metamizole) is a non-opioid analgesic commonly used in Germany, which can, in very rare cases, cause life-threatening agranulocytosis. The prescribing information calls for regular monitoring of the differential blood count in cases of long-term treatment. However, there is uncertainty about how this testing should be handled in practice. OBJECTIVES: Which recommendations can be derived from the published literature for evaluating blood cell counts during treatment with metamizole and which other options for monitoring exist? METHODS: Data from recent epidemiological studies, reviews, and spontaneously reported cases were evaluated...
October 20, 2016: Der Schmerz
(no author information available yet)
BACKGROUND: Significant safety concerns remain surrounding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) following gastrointestinal surgery, leading to wide variation in their use. This study aimed to determine the safety profile of NSAIDs after major gastrointestinal surgery. METHODS: Consecutive patients undergoing elective or emergency abdominal surgery with a minimum one-night stay during a 3-month study period were eligible for inclusion. The administration of any NSAID within 3 days following surgery was the main independent variable...
October 20, 2016: World Journal of Surgery
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