Managing intoxications with nicotine-containing e-liquids.

INTRODUCTION: Nicotine is an addictive and poisonous agent. The recent development of e-cigarettes has caused a new demand for highly concentrated nicotine-containing solutions. These concentrated nicotine solutions have also increased the risk of nicotine overdoses. AREAS COVERED: Essential factors for nicotine exposure are the concentration of the nicotine-containing e-liquid solution and its pharmacokinetics. Liquid nicotine refills contain nicotine in varying concentrations, which vary widely between and within products. The pharmacokinetics of nicotine are dependent on the route of administration, renal/hepatic clearance and urinary pH. The dose is another essential determinant of nicotine exposure. There is a considerable discrepancy between the generally accepted lethal dose and symptoms reported in case studies. Ingested doses correlate poorly to clinical symptoms. Symptoms of liquid nicotine toxicity vary from mild to severe between patients and are the result of overstimulation of nicotinic acetylcholine receptors, which may lead to fatal respiratory failure and cardiovascular collapse. EXPERT OPINION: The literature on nicotine-containing e-liquid intoxications originating from vaping device refills are mainly case reports. Based on these case reports, we propose a treatment plan which is primarily symptomatic. Research should focus on providing insight on its toxicity, based on oral and transdermal pharmacokinetics and on toxicodynamics.

The gastrointestinal microbiota in colorectal cancer cell migration and invasion.

Colorectal carcinoma is the third most common cancer in developed countries and the second leading cause of cancer-related mortality. Interest in the influence of the intestinal microbiota on CRC emerged rapidly in the past few years, and the close presence of microbiota to the tumour mass creates a unique microenvironment in CRC. The gastrointestinal microbiota secrete factors that can contribute to CRC metastasis by influencing, for example, epithelial-to-mesenchymal transition. Although the role of EMT in metastasis is well-studied, mechanisms by which gastrointestinal microbiota contribute to the progression of CRC remain poorly understood. In this review, we will explore bacterial factors that contribute to the migration and invasion of colorectal carcinoma and the mechanisms involved. Bacteria involved in the induction of metastasis in primary CRC include Fusobacterium nucleatum, Enterococcus faecalis, enterotoxigenic Bacteroides fragilis, Escherichia coli and Salmonella enterica. Examples of prominent bacterial factors secreted by these bacteria include Fusobacterium adhesin A and Bacteroides fragilis Toxin. Most of these factors induce EMT-like properties in carcinoma cells and, as such, contribute to disease progression by affecting cell-cell adhesion, breakdown of the extracellular matrix and reorganisation of the cytoskeleton. It is of utmost importance to elucidate how bacterial factors promote CRC recurrence and metastasis to increase patient survival. So far, mainly animal models have been used to demonstrate this interplay between the host and microbiota. More human-based models are needed to study the mechanisms that promote migration and invasion and mimic the progression and recurrence of CRC.