Research Publication Highlights
Amino-substituted 3-aryl- and 3-heteroarylquinolines as potential antileishmanial agents
Jared T Hammill , Vitaliy M Sviripa, Liliia M Kril, Diana Ortiz, Corinne M Fargo, Ho Shin Kim, Yizhe Chen, Jonah Rector, Amy L Rice, Malgorzata A Domagalska, Kristin L Begley, Chunming Liu, Vivek M Rangnekar, Jean-Claude Dujardin, David S Watt, Scott M Landfear, R Kiplin Guy
Combatting Leishmaniasis. Leishmaniasis is a neglected tropical disease caused by Leishmania parasites that are primarily spread by sand flies. Clinical evidence of infection often includes fever, weight loss, and abnormal blood cell counts, and in severe cases infection can be lethal. Current antileishmanial drugs are often associated with undesirable properties such as toxicity and increased resistance. Hammill et al. have identified and characterized a class of compounds called arylquinones with potent antileishmanial activity. Importantly, the arylquinones are structurally distinct in comparison to known antileishmanial drugs. Using a medicinal chemistry approach, a couple of early leads were identified that significantly improve upon the limitations of the current drug arsenal.
Evaluation of bivalirudin as the primary anticoagulant in patients receiving extracorporeal membrane oxygenation for SARS-CoV-2-sssociated acute respiratory failure
Pharmacists at the frontline of fighting COVID-19. Extracorporeal membrane oxygenation (ECMO) is an important approach for the management of severe acute respiratory failure secondary to COVID-19. However, its use in the context of the COVID-19 coagulopathy can lead to an increase in the incidence of venous thrombotic events. Optimal anticoagulation is therefore essential for an appropriate management of COVID-19 to reduce the risk of complications. This study added important information to the limited evidence thus far; it showed that bivalirudin administered under a pharmacist-driven dosing protocol can be a viable choice for anticoagulation in patients on ECMO for severe respiratory failure secondary to COVID-19.
Macrocyclic immunoproteasome inhibitors as a potential therapy for Alzheimer's disease
Designing better drugs. Alzheimer’s disease is a progressive brain disease that has limited treatment options and is ultimately fatal. A previous study identified the immunoproteasome as a new potential target, and a class of epoxyketones that inhibit the immunoproteasome were identified and shown to improve outcomes in a mouse model. In this report, Kim et al. design a second generation of epoxyketone inhibitors that have improved drug properties, thereby taking an important step toward translating the prior discoveries into a new drug therapy for Alzheimer’s disease.
Untargeted stable isotope probing of the gut microbiota metabolome using [13C]-labeled dietary fibers
Pan Deng, Taylor Valentino, Michael D Flythe, Hunter N B Mosely, Jacqueline R Leachman, Andrew J Morris, Bernhard Hennig
Microbiome meets metabolomics. Evidence for a vital role of the gut microbiome in human health continues to amass, however, the mechanisms by which microbes exert such consequential effects is complex and not well understood. Deng and coworkers report on the use of an isotope tracing methodology to track the metabolism of dietary fibers by the gut microbiome, revealing the ability of microbes to generate various metabolic products such as amino acids and vitamins that could potentially be used by the human host. Among other interesting results, a clear difference in metabolic efficiency was observed depending on the source of dietary fiber, thus expanding our understanding into the intricate connections between diet, the gut microbiome, and human health.
Association of phosphate containing solutions with incident hypophosphatemia in critically ill patients requiring continuous renal replacement therapy
Melissa L Thompson Bastin, Paul M Adams, Sethabhisha Nerusu, Peter E Morris, Kirby P Mayer, Javier A Neyra
Phosphate supplementation in critically ill patients. Hypophosphatemia, a common electrolyte disturbance in critically ill patients, can put them at additional risk and impact their prognosis. This electrolyte disturbance is an even more important issue in critically ill patients needing continuous renal replacement therapy (CRRT). The study sought to investigate whether using phosphate containing CRRT solutions would reduce the incidence of hypophosphatemia in critically ill patients. Investigators used existing data from medical records of 1,396 adult patients requiring CRRT during their intensive care unit stay and estimated an important reduction in the incidence of hypophosphatemia in patients treated with phosphate compared to those treated with non-phosphate containing CRRT solutions. This study provides important evidence to justify further randomized trials to fully investigate to role of phosphate containing CRRT solutions in the care of critically ill patients.
Development of single-stranded DNA bisintercalating inhibitors of primase DnaG as antibiotics
Bacterial resistance to antibiotics continues to decrease the utility of the current armament, and identifying new molecular targets has the potential to lead to the discovery of new antobiotcs that could help counter the resistance problem. Tsodikov and colleagues have characterized such a novel target, a DNA primase, and describe the synthesis of a new lead compound based on the topical agent dequalinium that has excellent DNA primase inhibitory activity.
Primary care clinician and community pharmacist perceptions of deprescribing
Understanding prescriber and pharmacist perceptions of deprescribing is essential to effectively promote this practice in efforts to reduce the use of inappropriate medications (i.e., those where risks outweigh benefits). This study, the first to directly compare primary care clinician and community pharmacist perceptions of deprescribing, identified important factors affecting the reported likelihood of deprescribing, including patient characteristics, time for counseling, communication, and trust within the clinician-patient-pharmacist triad. Interventions to support deprescribing should promote communication and trust within the triad and actively engage the patient in the process.
Chronic opioid use is associated with early biologic discontinuation in inflammatory bowel disease
Christian Rhudy, Courtney L Perry, Michael Singleton, Jeffery Talbert, Terrence A Barrett
Opiates called for interference. Patients suffering from inflammatory bowel disease (IBD) experience periods of exacerbation, or flares, accompanied by symptoms that often lead to emergency room visits and opioid prescriptions. Chronic opioid use complicates IBD management as it triggers a vicious circle; it further increases the susceptibility to flares and the clinical manifestations of opioid withdrawal. This study investigated the impact of chronic opioid use on the IBD treatment using biologic agents and found that patients that are opioid users are more likely to discontinue their treatment for IBD which negatively impacts the clinical management of their condition.
Clinical data mining reveals analgesic effects of lapatinib in cancer patients
Scientific Reports 2021, 11:3528 (February 11)
Shuo Zhou, Fang Zheng, Chang-Guo Zhan
A double-edged sword. Lapatinib, an FDA-approved anticancer drug, was recently shown to also have anti-inflammatory properties by targeting microsomal prostaglandin E2 synthase 1. Zhan and colleagues used a clinical data mining approach to reveal a significant reduction in various forms of pain for cancer patients treated with lapatinib. Thus, lapatinib has the potential to be repurposed for its analgesic properties.
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