BackgroundBrain tumor vasculature can be significantly compromised and leakier than that of normal brain blood vessels. Little is known if there are vascular permeability alterations in the brain adjacent to tumor (BAT). Changes in BAT permeability may also lead to increased drug permeation in the BAT, which may exert toxicity on cells of the central nervous system. Herein, we studied permeation changes in BAT using quantitative fluorescent microscopy and autoradiography, while the effect of chemotherapy within the BAT region was determined by staining for activated astrocytes.MethodsHuman metastatic breast cancer cells (MDA-MB-231Br) were injected into left ventricle of female NuNu mice. Metastases were allowed to grow for 28 days, after which animals were injected fluorescent tracers Texas Red (625 Da) or Texas Red dextran (3 kDa) or a chemotherapeutic agent 14C-paclitaxel. The accumulation of tracers and 14C-paclitaxel in BAT were determined by using quantitative fluorescent microscopy and autoradiography respectively. The effect of chemotherapy in BAT was determined by staining for activated astrocytes.ResultsThe mean permeability of texas Red (625 Da) within BAT region increased 1.0 to 2.5-fold when compared to normal brain, whereas, Texas Red dextran (3 kDa) demonstrated mean permeability increase ranging from 1.0 to 1.8-fold compared to normal brain. The Kin values in the BAT for both Texas Red (625 Da) and Texas Red dextran (3 kDa) were found to be 4.32 ± 0.2 × 105 mL/s/g and 1.6 ± 1.4 × 105 mL/s/g respectively and found to be significantly higher than the normal brain. We also found that there is significant increase in accumulation of 14C-Paclitaxel in BAT compared to the normal brain. We also observed animals treated with chemotherapy (paclitaxel (10 mg/kg), erubilin (1.5 mg/kg) and docetaxel (10 mg/kg)) showed activated astrocytes in BAT.ConclusionsOur data showed increased permeation of fluorescent tracers and 14C-paclitaxel in the BAT. This increased permeation lead to elevated levels of activated astrocytes in BAT region in the animals treated with chemotherapy.
Objective: To describe the safety, efficacy, and potential role in therapy of voclosporin, an oral calcineurin inhibitor approved by the Food and Drug Administration (FDA) in January 2021 as an adjunct treatment for lupus nephritis. Data Sources: A literature search was conducted using PubMed with the following terms: voclosporin, Lupkynis, and lupus nephritis (January 1, 2010, to December 1, 2021). FDA product labeling was also reviewed for pertinent data sources. Study Selection and Data Extraction: All articles were considered for inclusion. English-language articles selected included preclinical and clinical studies examining the pharmacokinetics, efficacy, and/or safety of voclosporin. Data Synthesis: Voclosporin has been studied as an adjunct immunosuppressive agent in patients with lupus nephritis. Drug design allows for a more predictable pharmacokinetic profile than other calcineurin inhibitors. Data suggest that adding this newly approved calcineurin inhibitor to a regimen of mycophenolate mofetil and corticosteroids produces promising therapeutic results. As such, voclosporin has been approved for use in patients with active lupus nephritis who are maintained on immunosuppressive therapy with mycophenolate mofetil and a corticosteroid. Relevance to Patient Care and Clinical Practice: Voclosporin may be a favorable calcineurin inhibitor in patients with lupus nephritis, due to a predictable pharmacokinetic profile. This allows for decreased therapeutic drug monitoring and suggests a favorable adverse effect profile. However, cost remains a consideration with this new agent. Conclusions: Current available data suggest that voclosporin is a promising adjunct treatment option for patients with active lupus nephritis who are maintained on mycophenolate mofetil and a corticosteroid.
Mnemonic devices are acronyms, abbreviations, or other learning tools that have been used for decades to memorize basic concepts. They are ubiquitous in teaching settings, including among intensive care unit (ICU) pharmacists, where the mnemonic FASTHUG (Feeding, Analgesia/Sedation, Thromboembolic prophylaxis, Head of bed, Ulcer prophylaxis, Glucose) is commonly cited. FASTHUG has existed since 2005 and serves as a reminder for key components of care for a critically ill patient. Due to the popularity of this acronym, multiple iterations have been created, where creative authors update, change, and/or add to the mnemonic. While FASTHUG is a unique learning tool with strengths for the entire care team, it has clear pitfalls when used in the pharmacy learning setting (i.e., during advanced practice rotations or for a postgraduate year 1 resident). This has led to the implementation of distinct mnemonic tools which are more specific to pharmacy interventions. The result is a myriad of published tools available for preceptors with limited data supporting their use in practice. A thorough understanding of the educational benefits of mnemonic devices paired with a recognition of their pitfalls can improve learning experiences. This review is designed to help preceptors understand the role of mnemonic devices and deploy them strategically for pharmacy learners. Furthermore, current pharmacy learners have different needs and characteristics when compared with other generations. This may alter the current students' level of comfort with utilizing mnemonics. Alternative teaching strategies that may be more beneficial for today's learners include technology and media utilization, scenario‐based discussions, and hands‐on application of mnemonics. Pharmacists who understand these variables can optimize their rotations and improve the learning experience for both themselves and their learners.
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