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Biomedical subjects

P Firby

Publications and source records attributed to P Firby.

5 recordsLinked to original sources
PubMed1996

Technetium-99m-tetrofosmin as a substrate for P-glycoprotein: in vitro studies in multidrug-resistant breast tumor cells.

UNLABELLED: The accumulation of 99mTc-tetrofosmin (TFos) was studied in wildtype (WT) and doxorubicin-resistant (AdrR) variants of the rat MatB and human MCF-7 breast tumor cell lines to determine whether TFos, like 99mTc-sestamibi (MIBI), is a substrate for P-glycoprotein (P-gp), a multidrug-resistance transporter. METHODS: The time course of accumulation of TFos and MIBI in WT and AdrR cells over 1 hr was studied using single-cell suspensions at 1 x 10(6) cells/ml incubated at 37 degrees C in the presence or absence of PSC833, a potent modulator of P-gp. Modulator dose-response curves were generated for PSC833, cyclosporin A, and verapamil. RESULTS: In both MatB and MCF-7 cells, TFos and MIBI accumulated extensively in WT cells and accumulation was not affected by PSC833. In contrast, ADrR cell lines accumulated very little of either tracer, but addition of PSC833 or other modulator increased this accumulation in a dose-dependent fashion. TFos and MIBI did not differ significantly in their behavior. CONCLUSION: TFos shares with MIBI the property of being a substrate for P-gp and thus TFos may be useful for functional imaging of tumor P-gp status.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

99Tcm-sestamibi as an agent for imaging P-glycoprotein-mediated multi-drug resistance: in vitro and in vivo studies in a rat breast tumour cell line and its doxorubicin-resistant variant.

Multi-drug resistance mediated by the transmembrane pump P-glycoprotein (Pgp) is an important mechanism of resistance of certain tumours against chemotherapeutic drugs. The myocardial perfusion imaging agent 99Tcm-sestamibi is a substrate for Pgp. Further characterization of 99Tcm-sestamibi has now been carried out in the transplantable rat breast adenocarcinoma cell line, MatB, and its doxorubicin-resistant variant, AdrR. In vitro accumulation of the tracer in wild-type (WT) MatB was high and was not affected by the Pgp modulator, PSC833. Conversely, AdrR cells did not accumulate significant amounts of tracer unless PSC833 was present. Imaging studies in rats bearing MatB-WT and AdrR tumours showed that 99Tcm-sestamibi washed out of the resistant tumours at three times the rate of WT tumours. These results support the potential use of 99Tcm-sestamibi for functional imaging of Pgp activity in patients undergoing chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Solid-phase extraction techniques for the determination of glycopyrrolate from equine urine by liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry.

Glycopyrrolate (Robinul) is a quaternary ammonium salt which serves as a respiratory enhancing drug. It is reportedly used in horse racing to improve breathing. Extraction of glycopyrrolate from equine urine employing unique solid-phase extraction techniques gave a residue suitable for liquid chromatography-tandem mass spectrometry (LC-MS-MS) and gas chromatography-mass spectrometry (GC-MS). LC-MS-MS analysis employed an extract derived from 5 ml of urine subjected to cation-exchange chromatography. The daughter ion of m/z 318 monitored in the positive-ion mode was m/z 116. Recovery of glycopyrrolate was 99.5% and the within-run coefficient of variation of two quality control samples (1.0 and 10 ng/ml) was less than 5%. The between-run coefficient of variation for the same two quality control samples was less than 6.5%. The minimal detectable concentration for the assay was 250 pg/ml. Due to the extremely low concentration of glycopyrrolate in urine, qualitative detection via full-scan GC-MS required XAD-2 extraction of 50 ml of urine, cation-exchange chromatography clean-up and a tandem hydrolysis-derivatization procedure. The target analyte for GC-MS qualitative analysis was the methyl ester of hydrolyzed glycopyrrolate. Glycopyrrolate could be detected in post-administration (1 mg intravenously) urine samples for up to 9 h by both LC-MS-MS and GC-MS. The success of the method was due to a combination of the extreme sensitivity of the LC-MS-MS method and the very selective extraction process for quaternary ammonium salts.

Animals↗
PubMed1989

Immediate hypersensitivity reactions in the guinea-pig conjunctiva: studies with a second-generation leukotriene D4 receptor antagonist, MK-571.

The role of leukotriene D4 (LTD4) as a mediator of immediate hypersensitivity reactions in the guinea-pig conjunctiva was examined using a potent, second-generation LTD4 receptor antagonist, MK-571 (also known as L-660,711). The microvascular permeability changes in the guinea-pig conjunctiva following challenge with either LTD4 or antigen were measured through accumulation of intravenously administered 99mtechnetium-labeled albumin. Topical application of MK-571 (up to 2 h pretreatment) significantly inhibited the conjunctival responses to LTD4 (ED50 of 18-60 ng/eye) but not to histamine. The responses to a single topical antigen challenge in ovalbumin-sensitized guinea pigs were significantly inhibited (44%) by topical treatment with MK-571, in contrast to the lack of effect previously observed with prototypic antagonists. The inhibitory effects of MK-571 did not involve an action on conversion of [3H]LTC4 to LTD4 and LTE4. Following a second antigen challenge (24 h after the first), MK-571 inhibited the resultant permeability changes by 78%. Specific histamine H1 and H2 antagonists similarly inhibited the responses to the first and second challenges (63 and 74%, respectively). The present study suggests that LTD4 is involved in conjunctival hypersensitivity reactions and that potent LTD4 receptor antagonists may be of therapeutic value in the treatment of allergic conjunctivitis.

Animals↗