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It is common practice to use cannulated rats for pharmacokinetic (PK) in-life studies as it yields high quality PK parameter estimation. While offering many benefits, cannulation requires surgery, post-surgical care, and cannula maintenance. As an alternative approach, the strategy of dosing and bleeding rats via the tail vein in a single experiment is technically feasible and theoretically offers many benefits. Unfortunately, however, as reported by F Tse et al. in 1984 (J Pharm Sci 73: https://doi.org/10.1002/jps.2600731128), parallel tail dosing and bleeding is scientifically flawed and yields inaccurate estimation of PK parameters following intravenous administration. The underlying causality of poor data quality has not been addressed in over 35 years. To overcome the technical flaws associated with parallel tail dosing and bleeding, we have developed a Tail-Dose-Bleed (TDB) method as a substitute for use of cannulated rats. Specifically, the method introduces a flush procedure after dosing, uses separate tail veins for dosing and bleeding, and adjusts dosing and sampling to the proximal and distal portions of the tail, respectively. To demonstrate the proof of principle for this TDB technique, several cassette dosing studies were conducted. The performance of the TDB technique is compared in both stand alone and animal crossover studies employing conventional jugular/femoral bleeding and dosing. The poor data via tail dosing and bleeding previously described by Tse et al. are also recapitulated using their described approach. To ensure broad applicability of the TDB technique, data were generated utilizing compounds of diverse physical chemical properties manifesting a range of clearance and/or volume of distribution characteristics. These data demonstrate that the TDB approach yields comparable PK profiles and parameters as compared to conventional femoral dosing / jugular bleeding. Using this newly described TDB procedure, we demonstrate the ability to overcome documented data quality issues when dosing and bleeding via the tail. The TDB technique has numerous operational advantages of reduced study turnaround time and improved cost effectiveness, but most importantly, addresses key animal welfare concerns relevant to institutional animal care and use committees (IACUC). The notable advantage here is reduced animal stress and discomfort by eliminating the need for surgery and recovery. And by consequence, allows for animals to be group housed and re-used without concern for loss of cannula patency. The tail dose and bleed method is simple and appears readily transferable to other laboratories.

Photography is one of the most important skills dentists need to master in order to perform esthetic dentistry at a high level. Today, digital single-lens reflex cameras are commonplace. Young dentists have grown up with Internet, smartphones, and online platforms exposing them, and their patients, to cases that other dentists have shared, increasing the awareness and popularity of esthetic-focused treatment. This article provides readers with a simplified and attainable approach to begin the dental photography journey, as well as increase skill level, depending on practice style and desired investment.

The objective of this article is to introduce the concept of branding to dentists interested in implementing elective esthetic treatment into their practice. For many, this will serve as an introduction to begin; for others, it can provide a road map for revising and reinforcing a branding program already in place.

Most drugs are intended to act on molecular targets residing within a specific tissue or cell type. Therefore, the drug concentration within the target tissue or cells is most relevant to its pharmacological effect. Increasing evidences suggest that drug transporters not only play a significant role in governing systemic drug levels, but are also an important gate keeper for intra-tissue and intracellular drug concentrations. This review focuses on polyspecific organic cation transporters, which include the organic cation transporters 1-3 (OCT1-3), the multidrug and toxin extrusion proteins 1-2 (MATE1-2) and the plasma membrane monoamine transporter (PMAT). Following an overview of the tissue distribution, transport mechanisms, and functional characteristics of these transporters, we highlight the studies demonstrating the ability of locally expressed OCTs to impact intracellular drug concentrations and directly influence their pharmacological and toxicological activities. Specifically, OCT1-mediated metformin access to its site of action in the liver is impacted by genetic polymorphisms and chemical inhibition of OCT1. The impact of renal OCT2 and MATE1/2-K in cisplatin intrarenal accumulation and nephrotoxicity is reviewed. New data demonstrating the role of OCT3 in salivary drug accumulation and secretion is discussed. Whenever possible, the pharmacodynamic response and toxicological effects is presented and discussed in light of intra-tissue and intracellular drug exposure. Current challenges, knowledge gaps, and future research directions are discussed. Understanding the impact of transporters on intra-tissue and intracellular drug concentrations has important implications for rationale-based optimization of drug efficacy and safety.