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The heart chamber of an adult Drosophila is approximately 2 mm long and 0.5 mm wide, and the interwall separation of different heart portions during systole and diastole range from tens of micrometers to hundreds of micrometers. Furthermore, the heart chamber has a curved structure, which results in the larger differences in depth between the different heart portions. However, applying the wavelength calibration process before Fourier transform in an optical coherence tomography (OCT) system may cause degradation in system sensitivity and longitudinal resolution when the optical path difference between the reference and sample arms increases, which makes imaging the entire heart chamber difficult with OCT system. Additionally, since the heartbeat rate of Drosophila is approximately 6 beats/s, a high-speed OCT system is necessary to record the dynamics of the heat beats. In this study, we propose a new approach to visualize the entire heart chamber including the conical chamber and four ostia portions, and to observe the retrograde and anterograde beats. A buffered Fourier-domain mode-locked (FDML) laser is implemented to provide a high imaging speed. Two output ports of the buffered FDML laser are used simultaneously to scan the different heart portions of Drosophila, and the effective A-scan rate of the OCT system can be doubled. Then, the two scanned images are merged into a single B-mode scan. Furthermore, with dual-beam OCT system, the beating behaviors of the different heart portions from 7-day-old and 21-day-old flies are compared. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Plant flavonoids are polyphenolic compounds commonly found in vegetables, fruits and many food sources that form a significant portion of our diet. These compounds have been shown to interact with several ATP-Binding Cassette transporters that are linked with anticancer and antiviral drug resistance and as such, may be beneficial in modulating drug resistance. The present study investigates the interactions of six common polyphenols; quercetin, silymarin, resveratrol, naringenin, daidzein and hesperetin with the multidrug resistance associated proteins, MRP1, MRP4 and MRP5. At non-toxic concentrations, several of the polyphenols were able to modulate MRP1-, MRP4- and MRP5- mediated drug resistance though to varying extents. The polyphenols also reversed resistance to NSC251820, a compound that appears to be a good substrate for MRP4 as had been predicted by data mining studies. Furthermore, most of the polyphenols showed direct inhibition of MRP1-mediated [3H]-dinitrophenyl S-glutathione and MRP4-mediated [3H]-cGMP transport in inside-out vesicles prepared from human erythrocytes. Additionally, both quercetin and silymarin were found to inhibit MRP1-, MRP4-, and MRP5-mediated transport from intact cells with high affinity. They also had significant effects on ATPase activity of MRP1 and MRP4 without having any effect on [α-32P]8-azidoATP binding to these proteins. This suggests that these flavonoids most likely interact at the transporter’s substrate-binding sites. Collectively, these results suggest that dietary flavonoids such as quercetin and silymarin can modulate transport activities of MRP1, 4 and 5. Such interactions could influence bioavailability of anticancer and antiviral drugs in vivo and thus, should be considered for increasing efficacy in drug therapies.

The nature of cGMP transport in human erythrocytes, its relationship to glutathione conjugate transport, and possible mediation by multidrug resistance-associated proteins (MRPs) have been investigated. MRP1, MRP4 and MRP5 are detected in immunoblotting studies with erythrocytes. MRP1 and MRP5 are also detected in multidrug resistant COR-L23/R and MOR/R cells but at greatly reduced levels in the parent, drug sensitive COR-L23/P cells. MRP4 is detected in MOR/R but not COR-L23/R cells. Uptake of cGMP into inside-out membrane vesicles prepared by a spontaneous, one-step vesiculation process is shown to be by a low affinity system that accounts for more than 80% of the transport at all concentrations above 3 micro m. This transport is reduced by MRP inhibitors and substrates including MK-571, methotrexate, estradiol 17-beta-d-glucuronide, and S(2,4-dinitrophenyl)glutathione (DNP-SG) and also by glibenclamide and frusemide but not by the monoclonal Ig QCRL-3 that inhibits high-affinity transport of DNP-SG by MRP1. It is concluded that the cGMP exporter is distinct from MRP1 and has properties similar to those reported for MRP4. Furthermore the evidence suggests that the protein responsible for cGMP transport is the same as that mediating low-affinity DNP-SG transport in human erythrocytes.