Non-Human Primate Models of Tuberculosis.

Among the animal models of tuberculosis (TB), the non-human primates, particularly rhesus macaques (Macaca fascicularis) and cynomolgus macaques (Macaca mulatta), share the greatest anatomical and physiological similarities with humans. Macaques are highly susceptible to Mycobacterium tuberculosis infection and manifest the complete spectrum of clinical and pathological manifestations of TB as seen in humans. Therefore, the macaque models have been used extensively for investigating the pathogenesis of M. tuberculosis infection and for preclinical testing of drugs and vaccines against TB. This review focuses on published major studies that exemplify how the rhesus and cynomolgus macaques have enhanced and may continue to advance global efforts in TB research.

(-)-Epigallocatechin-3-Gallate Enhances Hepatitis C Virus Double-Stranded RNA Intermediates-Triggered Innate Immune Responses in Hepatocytes.

(-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol component of green tea, has recently been identified as an inhibitor of hepatitis C virus (HCV) entry. Here, we examined whether EGCG can enhance hepatocyte-mediated intracellular innate immunity against HCV. HCV dsRNAs (Core, E1-P7, NS-3'NTR and NS5A) induced interferon-λ1 (IFN-λ1) expression in human hepatocytes. These HCV dsRNAs also induced the expression of Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I) and several antiviral IFN-stimulated genes (ISGs) expression. Although EGCG treatment of hepatocytes alone had little effect on TLR3 and RIG-I signaling pathways, EGCG significantly enhanced HCV dsRNAs-induced the expression of IFN-λ1, TLR3, RIG-I and antiviral ISGs in hepatocytes. Furthermore, treatment of HCV-infected hepatocytes with EGCG and HCV dsRNAs inhibited viral replication. Given that EGCG has the ability to enhance HCV dsRNAs-induced intracellular antiviral innate immunity against HCV, suggesting the potential application of EGCG as a new anti-HCV agent for HCV therapy.

Adverse Drug Event Prevention: 2014 Action Plan Conference.

Adverse drug events (ADEs) have been highlighted as a national patient safety and public health challenge by the National Action Plan for Adverse Drug Event Prevention (ADE Action Plan), which was released by the Office of Disease Prevention and Health Promotion in August 2014. The following October, the ADE Prevention: 2014 Action Plan Conference provided an opportunity for federal agencies, national experts, and stakeholders to coordinate and collaborate in the initiative to reduce preventable ADEs. The single-day conference included morning plenary sessions focused on the surveillance, evidence-based prevention, incentives and oversights, and additional research needs of the drug classes highlighted in the ADE Action Plan: anticoagulants, diabetes agents, and opioids. Afternoon breakout sessions allowed for facilitated discussions on measures for tracking national progress in ADE prevention and the identification of opportunities to ensure safe and high-quality health care and medication use.

Racial and Ethnic Disparities in Adverse Drug Events: A Systematic Review of the Literature.

The 2014 National Action Plan for Adverse Drug Event Prevention has recognized adverse drug events (ADEs) as a national priority in order to facilitate a nationwide reduction in patient harms from these events. Throughout this effort, it will be integral to identify populations that may be at particular risk in order to improve care for these patients. We have undertaken a systematic review to evaluate the evidence regarding racial or ethnic disparities in ADEs with particular emphasis on anticoagulants, diabetes agents, and opioids due to the clinical significance and preventability of ADEs associated with these medication classes. From an initial search yielding 3302 studies, we identified 40 eligible studies. Twenty-seven of these included studies demonstrated the presence of a racial or ethnic disparity. There was no consistent evidence for racial or ethnic disparities in the eight studies of ADEs in general. Asians were most frequently determined to be at higher risk of anticoagulant-related ADEs, and black patients were most frequently determined to be at higher risk for diabetes agents-related ADEs. Whites were most frequently identified as at increased risk for opioid-related ADEs. However, few of these studies were specifically designed to evaluate racial or ethnic disparities, lacking a standardized approach to racial/ethnic categorization as well as control for potential confounders. We suggest the need for targeted interventions to reduce ADEs in populations that may be at increased risk, and we suggest strategies for future research.

Monkey models of tuberculosis: lessons learned.

The use of animal models has been invaluable for studying the pathogenesis of Mycobacterium tuberculosis infection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. Among the applied animal models, nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. As such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. This review focuses on published major studies which illustrate how the rhesus and cynomolgus macaques have enriched and may continue to advance the field of global tuberculosis research.