Thioflavin T (ThT), a positively charged heterocyclic small molecule, is a widely used fluorescent marker of amyloid pathophysiology to confirm the cause of death in brain tissue of Alzheimer's disease (AD) patients. Literature precedents indicate that current positron emission tomography (PET) agents, such asC-PIB and F-flutemetamol, share significant structural similarity with ThT, a lipophilic dye which does not traverse the blood-brain barrier (BBB) to enable the detection of Aβ plaques. While vital for maintaining normal physiology and healthy brain function, the BBB comprises brain endothelial cells sealed paracellular protein complexes, bound by an extracellular matrix forming tight junctions thus controlling the delivery of molecules into the brain. The human P-glycoprotein (Pgp/ABCB1, 170 kD plasma membrane protein), belonging to the ABC family of efflux transporter proteins, also lines the luminal surface of brain endothelial cells thus poised to secrete its recognized substrates into the blood. Herein, we postulate that thioflavin T (ThT), due to its physico-chemical attributes, such as moderate lipophilicity and protonated nitrogen, could very well be recognized as a transport substrate of Pgp (P-glycoprotein, ABCB1) thus restricting its permeation into the brain. To evaluate whether or not ThT is indeed recognized by Pgp as its transport substrate thus limiting its BBB permeability, herein, we evaluate cellular accumulation profiles of ThT and PiB (a similar structural uncharged mimetic) in human epidermal carcinoma KB-3-1 (Pgp-) and MDR KB-8-5 (Pgp+) cells, using live-cell fluorescence imaging. While ThT penetrates KB-3-1 cells, it gets excluded from KB-8-5 cells, and also indicates LY335979-induced uptake in Pgp-expressing cells. Furthermore, the cellular uptake profiles of PiB are not impacted by the expression of Pgp under identical conditions. These data show that uptake profiles of ThT have been modified by the expression of Pgp in these cells, and are inversely proportional to the expression of the transporter protein located on the plasma membrane of these cells. Combined data demonstrate that ThT is efficiently recognized by Pgp as its transport substrate.

Background: Intravenous (IV) iron sucrose can be used for iron deficiency anemia (IDA), but little information exists on total dose infusion (TDI) of this drug. At a tertiary hospital, an iron sucrose TDI protocol was implemented with staff pharmacists aiding physicians in appropriate dosing. Objectives: We sought to define the safety and efficacy of this protocol in adults ≥18 years old with IDA. Methods: We conducted a retrospective chart review of patients who received iron sucrose TDI. Inclusion criteria included patients ≥18 years old who were hospitalized and received iron sucrose in doses ≥300 mg. We reviewed the medical record for adverse reactions to any TDI of iron sucrose as well as pre-TDI and post-TDI hemoglobin (Hgb) levels to assess efficacy. Results: A total of 238 patients received iron sucrose TDI for IDA during the study period. One hundred ninety-three (81%) patients were female, and the mean age in our cohort was 60.6 years. Mean pre-TDI Hgb was 8.76 g/dL. The mean total dose of iron sucrose in the total cohort was 680 mg (range: 300-2500 mg). Adverse effects attributable to iron sucrose were reported in 15 patients, with nausea being the most common effect (7/238, 2.9%). When matching patients’ preadmission and postadmission records, a Hgb increase of 2.1 g/L was found ( P < .001). No increase in liver function tests was found in any patient. Conclusions: A pharmacist-assisted iron sucrose TDI protocol for patients with IDA successfully increased serum Hgb and was well tolerated. Anaphylaxis was not reported.

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