Why Assuring the Quality of Antimicrobials Is a Global Imperative.

Poor-quality antimicrobial medicines continue to proliferate across supply chains, threatening patients' health and safety, especially in low- and middle-income regions. This article discusses consequences and risks of antimicrobial resistance and other ways in which antimicrobial medicines can be of poor quality and recommends regulatory and policy reforms to help maintain supply chain resilience and quality of antimicrobial medicines.

How Should Regulators and Manufacturers Prevent Avoidable Deaths of Children From Contaminated Cough Syrup?

This commentary responds to a case about diethylene glycol-contaminated glycerin in cough syrup. Glycerin is a commonly used excipient in medicines to improve texture and taste. Excipients are typically pharmacologically inactive ingredients contained in prescription and over-the-counter drugs that play a critical role in the delivery, effectiveness, and stability of active drug substances.

Which Drugs Should Be on the Essential Medicines List?

The World Health Organization (WHO) published its first Essential Medicines List (EML) in 1977, and it is updated biennially. One might reasonably think drugs on the EML are there because they are critical to effective, evidence-based patient care and intervention. One might not reasonably guess, however, that a particular drug's supply chain vulnerabilities that make it a shortage risk would contribute to a drug's listing on the EML.

Seven Points for Athletes to Consider Before Using a Dietary Supplement.

Performance-enhancing drugs (PEDs) have been used by athletes for as long as sporting competitions have existed. To protect the health and safety of athletes and promote fair play, banned substance lists were developed that include several classes of PEDs. Evidence shows that a majority of athletes use dietary supplement products to aid their training and support their health.

Which Features of Dietary Supplement Industry, Product Trends, and Regulation Deserve Physicians' Attention?

Patients expect that dietary supplements they purchase-and physicians expect that dietary supplements they recommend-are safe, accurately labeled, quality products. Since many dietary supplements, especially vitamins and minerals, are key parts of evidence-based interventions for patients with many conditions, illegal, fraudulent, adulterated, or improperly labeled products should be regarded as sources of clinical and ethical concern. Adverse events (AEs) can occur and, when they do, relevant data should be carefully collected and analyzed.

What Should Dietary Supplement Oversight Look Like in the US?

Most American adults who use dietary supplements (eg, vitamins, minerals, plant and animal extracts, hormones, and amino acids) ingest them orally. The market for these products has grown rapidly and significantly over the last 25 years, but consumer protection regulations have not kept pace. In the United States, supplements' safety is regulated by the US Food and Drug Administration (FDA), but statutory limitations prevent the FDA from effectively regulating these products, exacerbate public health risk, and have generated numerous calls for reform.

Position Paper: Recommendations for the Investigation, Diagnosis, and Certification of Deaths Related to Opioid and Other Drugs.

The National Association of Medical Examiners convened an expert panel to update the association's evidence-based recommendations for investigating and certifying deaths associated with opioids and other misused substances to improve death certificate and mortality data for public health surveillance. The recommendations are as follows:1. Autopsy provides the best information on a decedent's medical condition for optimal interpretation of toxicology results, circumstances surrounding death, medical history, and scene findings.

The Opioid Epidemic: Moving Toward an Integrated, Holistic Analytical Response.

In many jurisdictions, public safety and public health entities are working together to enhance the timeliness and accuracy of the analytical characterization and toxicology testing of novel synthetic opioids. The improved sharing and early detection of these analytical data are intended to inform surveillance, interdiction efforts, patient intervention and treatment, all of which are critical to curbing the opioid epidemic. Forensic practitioners working to identify novel synthetic opioids struggle to provide timely results when encountering new or unknown substances, such as the fentanyl analogs.

Swift and Certain, Proportionate and Consistent: Key Values of Urine Drug Test Consequences for Probationers.

Traditionally, urine drug testing (UDT) in the correctional population (both prison and community corrections) has been infrequent, is scheduled, and has a high possibility of delayed results. Of practical relevance is that scheduled testing is ineffective for identifying drug misuse. Of ethical relevance is that consequences of positive scheduled tests can be unpredictable-in the form of overly severe punishment or a lack of treatment options-and that the scheduled testing paradigm is a poor way to change behaviors.

Performance-Enhancing Drugs I: Understanding the Basics of Testing for Banned Substances.

Whenever athletes willfully or accidentally ingest performance-enhancing drugs or other banned substances (such as drugs of abuse), markers of those drugs can be detected in biological samples (e.g., biofluids: urine, saliva, blood); in the case of some drugs, that evidence can be apparent for many weeks following the last exposure to the drug.

Mechanism of error caused by isotope-labeled internal standard: accurate method for simultaneous measurement of vitamin D and pre-vitamin D by liquid chromatography/tandem mass spectrometry.

Rationale: Bias of up to 25% has been observed for vitamin D3 and D2 samples exposed to heating during sample preparation, even when isotope-labeled internal standards are used. The goals of this study were to identify the mechanism of the positive bias observed in measuring vitamin D3 and D2 by liquid chromatography/tandem mass spectrometry (LC/MS/MS) and determine a way to eliminate the error source.

Methods: Several internal standards with varying locations of labeling were used for comparison in this study.

The androgen receptor and its use in biological assays: looking toward effect-based testing and its applications.

Steroid abuse is a growing problem among amateur and professional athletes. Because of an inundation of newly and illegally synthesized steroids with minor structural modifications and other designer steroid receptor modulators, there is a need to develop new methods of detection which do not require prior knowledge of the abused steroid structure. The number of designer steroids currently being abused is unknown because detection methods in general are only identifying substances with a known structure.

Toxicological determination and in vitro metabolism of the designer drug methylenedioxypyrovalerone (MDPV) by gas chromatography/mass spectrometry and liquid chromatography/quadrupole time-of-flight mass spectrometry.

A method for the toxicological screening of the new designer drug methylenedioxypyrovalerone (MDPV) is described; with an emphasis on its application for anti-doping analysis. The metabolism of MDPV was evaluated in vitro using human liver microsomes and S9 cellular fractions for CYP450 phase I and uridine 5'-diphosphoglucuronosyltransferase (UGT) and sulfotransferase (SULT) phase II metabolism studies. The resulting metabolites were subsequently liquid/liquid extracted and analyzed using gas chromatography/mass spectrometry (GC/MS) as trimethylsilyl (TMS) derivatives.

The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: pharmacology, toxicology and analysis.

Diuretics are drugs that increase the rate of urine flow and sodium excretion to adjust the volume and composition of body fluids. There are several major categories of this drug class and the compounds vary greatly in structure, physicochemical properties, effects on urinary composition and renal haemodynamics, and site and mechanism of action. Diuretics are often abused by athletes to excrete water for rapid weight loss and to mask the presence of other banned substances.

Effect of anabolic-androgenic steroids and glucocorticoids on the kinetics of hAR and hGR nucleocytoplasmic translocation.

Although the qualitative nucleocytoplasmic transport of nuclear hormone receptors (NHRs) has been studied, there is little documentation of the cellular kinetics of this transport. Here, translocation studies using the human androgen receptor (hAR) and the human glucocorticoid receptor (hGR) were performed to aid in identifying the mechanism by which anabolic-androgenic steroids (AAS) were activating hAR and potentially interacting with hGR and how glucocorticoid ligands were interacting with the hGR and hAR. The real-time analysis of EGFP-labeled hAR and hGR ligand-induced cytoplasm-to-nucleus translocation was performed using fluorescence microscopy to better understand the action of these NHRs in a physiologically relevant cell-based model.

Signal sequences for targeting of gene therapy products to subcellular compartments: the role of CRM1 in nucleocytoplasmic shuttling of the protein switch.

Purpose: The purpose of this study was to understand the mechanism of nuclear export of the protein switch, used for controlled intracellular delivery of gene products, by studying the involvement of classical export receptor CRM1.

Method: Transient transfections of protein switch constructs, isolated nuclear export and import signals were carried out. Effect of leptomycin B (inhibitor of export receptor) and geldanamycin (inhibitor of Hsp90) on localization of these constructs was studied using fluorescence microscopy.