Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

The infantile cutaneous microbiome: A review

Recent focus on the neonatal intestinal microbiome has advanced our knowledge of the complex interplay between the intestinal barrier, the developing immune system, and commensal and pathogenic organisms. Despite the parallel role of the infant skin in serving as both a barrier and an interface for priming the immune system, large gaps exist in our understanding of the infantile cutaneous microbiome. The skin microbiome changes and matures throughout infancy, becoming more diverse and developing the site specificity known to exist in adults. Delivery method initially determines the composition of the cutaneous microbiome, though this impact appears transient. Cutaneous microbes play a critical role in immune system development, particularly during the neonatal period, and microbes and immune cells have closely intertwined, reciprocal effects. The unique structure of newborn skin influences cutaneous microbial colonization and the development of dermatologic pathology. The development of the infantile skin barrier and cutaneous microbiome contributes to future skin pathology. Atopic dermatitis flares and seborrheic dermatitis have been linked to dysbiosis, while erythema toxicum neonatorum is an immune response to the establishment of normal bacterial skin flora. Physicians who care for infants should be aware of the impact of the infantile skin microbiome and its role in the development of pathology. A better understanding of the origin and evolution of the skin microbiome will lead to more effective prevention and treatment of pediatric skin disease.     

A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

OTC drug advertising in Japan: the role of need for cognition and celebrity endorser credibility

Abstract

This research explores how the level of consumers’ need for cognition (NFC) is associated with celebrity endorser credibility and examines its effects on advertising-related attitudes. A 3 (endorser types: actor/actress, athlete, TV personality/talent) × 2 (endorser’s gender) factorial experiment with 435 Japanese consumers was conducted. Concerning Japanese OTC drug advertising, lower NFC individuals perceived celebrity endorsers as more credible in comparison to higher NFC individuals. The main effects of NFC and endorser type on endorser credibility existed; however, no interaction between the two variables was found. The endorser type had an influence on attitudes toward ads and the advertised brand.     

Immune checkpoint inhibitor-induced inflammatory arthritis: identification and management

ABSTRACT

Introduction

Immune checkpoint inhibitors (ICIs) have proved to be groundbreaking in the field of oncology. However, immune system overactivation from ICIs has introduced a novel medical entity known as immune-related adverse events (irAEs), that can affect any organ or tissue. ICI-induced inflammatory arthritis (ICI-IIA) is the most common musculoskeletal irAE and can lead to significant morbidity and limitation in anti-cancer therapy.