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Find video protocols related to scientific articles indexed in Pubmed.
Nonaqueous gel for the transdermal delivery of a DTPA penta-ethyl ester prodrug.
AAPS J
PUBLISHED: 01-17-2013
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Diethylenetriamine pentaacetic acid penta-ethyl ester, designated as C2E5, was successfully incorporated into a nonaqueous gel for transdermal delivery. The thermal and rheological properties of a formulation containing 40% C2E5, 20% ethyl cellulose, and 40% Miglyol 840® prepared using the solvent evaporation method demonstrated that the gel had acceptable content uniformity and flow properties. In vitro studies showed that C2E5 was steadily released from the gel at a rate suitable for transdermal delivery. Topical application of the gel at a 200 mg C2E5/kg dose level in rats achieved significantly higher plasma exposures of several active metabolites compared with neat C2E5 oil at the same dose level. The results suggest that transdermal delivery of a chelator prodrug is an effective radionuclide decorporation strategy by delivering chelators to the circulation with a pharmacokinetic profile that is more consistent with the biokinetic profile of transuranic elements in contaminated individuals.
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Organic anion transporting polypeptides in the hepatic uptake of PBDE congeners in mice.
Toxicol. Appl. Pharmacol.
PUBLISHED: 05-17-2011
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BDE47, BDE99 and BDE153 are the predominant polybrominated diphenyl ether (PBDE) congeners detected in humans and can induce drug metabolizing enzymes in the liver. We have previously demonstrated that several human liver organic anion transporting polypeptides (humans: OATPs; rodents: Oatps) can transport PBDE congeners. Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. However, the mechanism of the hepatic PBDE uptake in mice is not known. Therefore, the purpose of the current study was to test the hypothesis that BDE47, BDE99, and BDE153 are substrates of mouse hepatic Oatps (Oatp1a1, Oatp1a4, Oatp1b2, and Oatp2b1). We used Human Embryonic Kidney 293 (HEK293) cells transiently expressing individual Oatps and quantified the uptake of BDE47, BDE99, and BDE153. Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners, whereas Oatp1a1 did transport none. Kinetic studies demonstrated that Oatp1a4 and Oatp1b2 transported BDE47 with the greatest affinity, followed by BDE99 and BDE153. In contrast, Oatp2b1 transported all three PBDE congeners with similar affinities. The importance of hepatic Oatps for the liver accumulation of BDE47 was confirmed using Oatp1a4-, and Oatp1b2-null mice.
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Mechanism of polybrominated diphenyl ether uptake into the liver: PBDE congeners are substrates of human hepatic OATP transporters.
Toxicol. Sci.
PUBLISHED: 02-22-2010
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Polybrominated diphenyl ethers (PBDEs) are flame-retardants that upon chronic exposure enter the liver where they are biotransformed to potentially toxic metabolites. The mechanism by which PBDEs enter the liver is not known. However, due to their large molecular weights (MWs approximately 485 to 1000 Da), they cannot enter hepatocytes by simple diffusion. Organic anion-transporting polypeptides (OATPs) are responsible for hepatic uptake of a variety of amphipathic compounds of MWs larger than 350 Da. Therefore, in the present study, Chinese hamster ovary cell lines expressing OATP1B1, OATP1B3, and OATP2B1 were used to test the hypothesis that OATPs expressed in human hepatocytes would be responsible for the uptake of PBDE congeners 47, 99, and 153. The results demonstrated that PBDE congeners inhibited OATP1B1- and OATP1B3-mediated uptake of estradiol-17-beta-glucuronide as well as OATP2B1-mediated uptake of estrone-3-sulfate in a concentration-dependent manner. Direct uptake studies confirmed that all three PBDE congeners are substrates for the three tested hepatic OATPs. Detailed kinetic analysis revealed that OATP1B1 transported 2,2,4,4-tetrabromodiphenyl ether (BDE47) with the highest affinity (K(m) = 0.31 microM) followed by 2,2,4,4,5-pentabromodiphenyl ether (BDE99) (K(m) = 0.91 microM) and 2,2,4,4,5,5-hexabromodiphenyl ether (BDE153) (K(m) = 1.91 microM). For OATP1B3, the order was the same (BDE47: K(m) = 0.41 microM; BDE99: K(m) = 0.70 microM; BDE153: K(m) = 1.66 microM), while OATP2B1 transported all three congeners with similar affinities (BDE47: K(m) = 0.81 microM; BDE99: K(m) = 0.87 microM; BDE153: K(m) = 0.65 microM). These results clearly suggest that uptake of PBDEs via these OATPs is a mechanism responsible for liver-specific accumulation of PBDEs.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.